Researchers globally produce hundreds of thousands of studies annually. It can be difficult to know if at some time in the future they will be the foundation for a disease cure or a technology such as CRISPR that revolutionizes medicine. But many are exciting for what they point to or how they spike the imagination. Heres a look at 10 of the more compelling research stories of the year.

Type 1 Diabetes Therapy Showed Promise in Early-Stage Trial

Vertex Pharmaceuticalsannouncedpositive early data from the first patient in its Phase I/II study of VX-880 in type 1 diabetes (T1D). The therapy is a stem cell-derived, fully differentiated pancreatic islet cell replacement therapy. T1D is an autoimmune disease, where the immune system attacks the islet cells in the pancreas, which is where insulin is produced. This leads to loss of insulin production and problems with blood sugar control.

In the study, the patient received a single infusion of VX-880 at half the target dose along with immunosuppressive therapy. The patient showed successful engraftment and demonstrated fast and robust improvements in several measurements, including increases in fasting and stimulated C-peptide, improvements in glycemic control, including HbA1c. It also resulted in less need for medical insulin. The therapy appeared well tolerated.

Some Alzheimers Plaques May Be Protective

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One of the hallmarks of Alzheimers disease is the buildup of beta-amyloid plaques in the brain. Yet many drugs that cleared amyloid dont seem to improve memory or cognition. Many researchers believe amyloid is only part of the issue, perhaps triggering inflammation that causes damage to the brain. New research out of theSalk Instituteadded a new twist, suggesting that some of the plaques may be protective. A type of immune cell in the brain, microglia, was long believed to inhibit the growth of plaques by eating them. Their research, however, demonstrated that microglia promote the formation of what are being dubbed dense-core plaques, which transports the wispy plaque away from neurons. They published their research in the journalNature Immunology.

We show that dense-core plaques dont form spontaneously, said Greg Lemke, a professor in Salks Molecular Neurobiology Laboratory. We believe theyre built by microglia as a defense mechanism, so they may be best left alone. There are various efforts to get the FDA to approve antibodies whose main clinical effect is reducing dense-core plaque formation, but we make the argument that breaking up the plaque may be doing more damage.

5 Genes Associated with Lewy Body Dementia, with Implications for Alzheimers and Parkinsons

Research conductedby theNIHs National Institute of Neurological Disorders and Stroke (NINDS)identified five genes that appear to play a critical role in whether a person will suffer from Lewy body dementia, a type of dementia where the brain accumulates clumps of abnormal protein deposits known as Lewy bodies. The data also supported Lewy body dementias connections to Parkinsons disease and connections to Alzheimers disease. The research was published in the journalNature Genetics.

Sonja Scholz, investigator at the NIHs NINDS and senior author of the study, said, Our results support the idea that this may be because Lewy body dementia is caused by a spectrum of problems that can be seen in both disorders. We hope that these results will act as a blueprint for understanding the disease and developing new treatments.

Why Obesity is Associated with Inflammation

Although obesity is linked with many inflammatory conditions, including cancer, diabetes, heart disease, and infection, why isnt it well understood? Researchers atUT Southwestern Medical Centeridentifieda type of cell that, at least in mice, is responsible for triggering inflammation in fat tissue. In obese individuals, white adipose tissue (WAT), stores excess calories in the form of triglycerides. In obesity, WAT is overworked, fat cells start to die, and immune cells are activated. The research team identified an adipose progenitor cell (APC), a precursor that later generates mature fat cells. These new cells are called fibro-inflammatory progenitors (FIPs) and they make signals that encourage inflammation.

Whats Behind Brain Fog in COVID-19 Patients

One of several unusual symptoms reported in COVID-19 patients is what is dubbed brain fog or COVID brain, but in medical terminology, is called encephalopathy. It appears to be loss of short-term memory, headaches and confusion. At its most severe, it is associated with psychosis and seizures. Researchers atMemorial Sloan Kettering Cancer Centerpublishedresearch in the journalCancer Cellthat explains the underlying cause of brain fog.

Jan Remsik, a research fellow in the lab, says, We found that these patients had persistent inflammation and high levels of cytokines in their cerebrospinal fluid, which explained the symptoms they were having.

New Compound Appears to Reverse Neuron Damage Caused by ALS

Researchers atNorthwestern Universityidentifieda compound that appears to reverse the ongoing degeneration of upper motor neurons associated with amyotrophic lateral sclerosis (ALS). ALS is a progressive neurodegenerative disease affecting nerve cells in the brain and spinal cord. As the motor neurons degenerate, they eventually die and the ability of the brain to initiate and control muscle movement is lost. With the disease, people may lose the ability to speak, eat, move and breathe. The compound, NU-9, was developed in the laboratory of Richard B. Silverman, the Patrick G. Ryan/Aon Professor of Chemistry at Northwestern. It can reduce protein misfolding in critical cell lines. The compound is also not toxic and can cross the blood-brain barrier. They published their research inClinical and Translational Medicine.

How Astrocytes Fix Damage in the Brain

Investigators withCharit Universittsmedizin Berlindescribed how a type of glial cell, called astrocytes, plays a role in protecting surrounding brain tissue after damage. They become part of a defense mechanism called reactive astrogliosis, which helps form scars, and contains inflammation and controls tissue damage. Astrocytes are also able to ensure the nerve cells survive that are located immediately next to the tissue injury, which preserves the function of neuronal networks. The mechanism was the protein drebrin, which controls astrogliosis. Astrocytes require drebrin to form scars and protect the surrounding tissue. Drebrin regulates the reorganization of the actin cytoskeleton, an internal scaffold that maintains astrocyte mechanical stability.

A New Spin on Jurassic Park?

In the books and filmsJurassic Park, researchers collected the blood from insects trapped in amber and cloned dinosaurs. A researcher from theUniversity of Minnesota is putting a more practical spin on amber research. Amber is the fossilized resin from a now-extinct species of pine, Sciadopityaceae. It was formed about 44 million years ago. In the Baltic regions, amber has been used for hundreds of years for traditional medicines for pain relief and its anti-inflammatory and anti-infective properties. Previous research has suggested that amber molecules might have an antibiotic effect. The team extracted even more chemicals from amber samples that appeared to show activity against gram-positive, antibiotic resistant bacteria.

They identified 20 compounds using GC-MS in the amber, most prominent being abietic acid, dehydroabietic acid and palustric acid, compounds with known biological activity. They also acquired a Japanese umbrella pine, the closest living species to theSciadopityaceae, and extracted resins and identified sclarene, a molecule present in the amber extracts that could potentially undergo chemical transformations to produce the bioactive molecules found in the Baltic amber samples.

The most important finding is that these compounds are active against gram-positive bacteria, such as certain Staphylococcus aureus strains, but not gram-negative bacteria, said Connor McDermott, a graduate student in the laboratory of Elizabeth Ambrose, who led the research. This implies the composition of the bacterial membrane is important for the activity of the compounds.

Genetics of People Who Live 105 or Older

A new study of 81 semi-supercentenarianspeople 105 years of age or olderand supercentenarians110 years or older from across Italy, werestudiedby researchers from theUniversity of Bologna, Italy andNestle Research in Lausanne, Switzerland. They compared genetic data from these extraordinary agers to 36 healthy people from the same region whose age, on average, was 68 years. Blood samples were drawn, and whole-genome sequencing was performed. They then compared their data with another previously published study that analyzed 333 Italians over 100 years of age and 358 people who were about 60 years of age. They published their research in the journal eLife.

Scientists identified five common genetic changes that were most frequent in the 105+/110+ groups, between two genes known as COA1 and STK17A. Analysis showed the same variants in the people over 100. Computational analysis predicted these variations most likely modulated the expression of three different genes: STK17A, COA1 and BLVRA.

Junk DNA and Aging

For a long time, so-called junk DNA was thought to play no role in inheritance or metabolism. Increasingly, this non-coding DNA is found to play a significant role in gene regulation. Researchers atWashington State Universityrecently identifieda DNA region called VNTR2-1 that seems to drive telomerase gene activity. In addition, it appears to prevent aging in some types of cells. Telomeres are the ends of chromosomes, and their length is associated with aging that is to say, as the older you get, the shorter they get because every time cells divide, the telomeres get a tiny bit shorter. When they get too short, cells no longer reproduce. But in some reproductive cells and cancer cells, telomerase gene activity resets telomeres to the same length when DNA was originally copied, creating a kind of immortality for those cells.

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As 2021 draws to a close, COVID-19 remains a pervasive influence over life at Yale and across the world. And yet, even as a new surge in cases portends a winter of uncertainty, a look back at the past year offers many reminders of just how much more we now know about this global threat, the remarkable importance of vaccines and other public health measures, and the resiliency of humankind.

After reviewing the many hundreds of stories published on Yale News this year, we identified several about Yales response to the pandemic that especially resonated with readers and that best capture how the university and our experts have helped make sense of and respond to this disruptive disease. Youll find a list below.

In a second list below, we highlight several non-COVID stories about the people and projects that inspired us and gave us hope for a healthier and more equitable 2022 and the new initiatives that will position the Yale community to be a leader in tackling the challenges of the future.

As the new year began, Yale News reviewed how the campus community pulled together to do the work of the university in the face of unprecedented challenges, and looked ahead to the spring semester.

As chair of the White Houses COVID-19 Equity Task Force, Dr. Marcella Nunez-Smith, the C.N.H Long Professor of Internal Medicine, Public Health, and Management at Yale, became a national voice on racial inequities in COVID-19 treatment and outcomes. Meanwhile, Abbe Gluck, the Alfred M. Rankin Professor of Law and professor of internal medicine at Yale School of Medicine, was named special counsel to the Biden administrations COVID-19 Response team. She also worked in the Office of White House Counsel on other health care issues, including the Affordable Care Act..

In early January, Yale launched its COVID-19 vaccination program in the Lanman Center at Payne Whitney Gymnasium, as vaccines from Moderna and Pfizer gained final approvals for use in the United States.

After spending nearly a year cataloguing and exploring the SARS-CoV-2 genomes intricate makeup, a team of Yale scientists revealed a map of it with an unprecedented level of detail, including more than 100 identifiable structures.

In February, Yale scientists developed a new class of antiviral agents that showed promise for creating COVID-19 therapeutics exhibiting particular effectiveness when used in tandem with the drug remdesivir, another antiviral medication approved for use against the virus.

For most children, COVID-19 infection results in a relatively mild illness. In a few cases, however, a severe immune reaction occurs. During the spring, Yale research found that such rare, life-threatening reactions may be triggered by high levels of alarmins, molecules that make up part of the innate immune system.

The Lanman Center, which early in the pandemic was converted into a field hospital, and later into Yales primary vaccination center, returned to being simply a gym during the summer, as the vaccination operations were shifted to the Rose Center on Ashmun Street.

In July, a Yale-led study found that the COVID-19 vaccination campaign launched in the United States in late 2020 had, at that point, saved some 279,000 lives and prevented 1.25 million hospitalizations. Researchers warned, however, that these gains could be reversed by the highly transmissible Delta variant.

In September, Yale researchers provided important insights into what were then becoming known as breakthrough COVID-19 cases in which fully vaccinated individuals are infected by SARS-CoV-2 and which populations are particularly vulnerable to serious breakthrough illness.

Since the start of the COVID-19 pandemic, scientists had been unclear about how long immunity lasts after an unvaccinated person is infected. In October, a Yale-led team of researchers found an answer: Strong protection following natural infection is short-lived, lasting as little as three months or less.

In October, a Yale-led study found that two of the commonly used COVID-19 vaccines provide protection against multiple variants of the virus that causes the disease, including the highly infectious Delta variant. Their findings also showed that those infected with the virus prior to vaccination exhibit a more robust immune response to all variants than those who were uninfected and fully vaccinated.

In November, a study by Yale political scientists and public health experts found that, when it comes to persuading people to get vaccinated against COVID-19, its more effective to appeal to community spirit than to self-interest.

Breakthrough SARS-CoV-2 infections tend to be mild, but Yale research published in December showed that more older adults have developed severe breakthrough cases during the Delta variant phase of the pandemic, particularly after a longer period of time had elapsed since their last vaccination. The findings, researchers say, reveal the importance of booster vaccinations.

White evangelical Christians have resisted getting vaccinated against COVID-19 at higher rates than other religious groups in the U.S. In November, a Yale study found that persuading these vaccine holdouts had only become more difficult.

In December, as a new COVID-19 variant, Omicron, began to spread throughout the world, public health leaders scrambled to better understand how contagious the new variant is and whether existing vaccines are effective against it. Yale doctors offered insights into the emerging threat.

In February, Yale announced the establishment of the Wu Tsai Institute, an ambitious new research enterprise that will supercharge Yales neuroscience initiative and position the university to reveal the brain in its full, dynamic complexity, thanks to a historic gift from Joseph C. Tsai 86, 90 J.D. and his wife, Clara Wu Tsai.

As a historic renovation of the Peabody Museum proceeds, conservator Mariana Di Giacomo is charged with keeping a close eye on the iconic mural The Age of Reptiles, by celebrated artist Rudolph Zallinger. The experience has allowed her to appreciate layers of detail. In February, Yale News caught up with her and shared a dazzling gallery of images.

In a promising early trial, researchers from Yale reported in February that patients with spinal cord injuries experienced substantial improvements in motor function such as the ability to walk or to use their hands after an intravenous injection of bone marrow-derived stem cells.

After 30 months of renovations, the redesigned Humanities Quadrangle formerly the Hall of Graduate Studies put a vibrant new face on Yales longstanding excellence in the humanities. The refurbished building includes dynamic spaces that promote connections among departments and programs and the cultivation of new ideas.

The late Jeremy Ayers once known as the gender-bending performance artist Silva Thin may seem like an unlikely namesake for an ant. But thanks to Yale ecologist Douglas B. Booher and rock star Michael Stipe, who shared a decades-long friendship with Ayers, a new species from the forests of Ecuador will honor his legacy and his reverence for the diversity of life.

During the summer, the university announced that present and future students at Yale Universitys drama school will no longer pay tuition, thanks to a landmark $150 million gift from entertainment executive and philanthropist David Geffen.

Psilocybin, a psychedelic drug found in some mushrooms, has long been studied as a potential treatment for depression. Yale research published in July detailed exactly what happens in the brain after a dose of psilocybin, and what makes its medicinal properties so promising.

In August, Yale scientists published a study of atmospheric patterns on Mars and Saturns moon Titan that will help lay the foundation for more accurate forecasts of weather on other worlds. Researchers say such forecasts will be vital to the safety and success of future research missions.

In 1965, Yale scholars created a sensation with the revelation of the Vinland Map, which was thought to be the earliest known European depiction of the New World. This summer, a team of Yale researchers said it proved the map to be an elaborate 20th-century forgery.

In October, a series of performances by the Yale Glee Club, Yale Bands, and the Yale Symphony Orchestra held in each of Yales residential college courtyards marked a return to live music on campus following a year of lockdowns and a response to the Black Lives Matter protests of 2020. (With video.)

In November, Yale and the City of New Haven reconfirmed their historic, three-century partnership for a new generation, announcing a six-year commitment that increases the universitys annual voluntary financial contribution to the city and creates bold opportunities for inclusive economic growth that benefit the entire community.

Tony Reno, now in his ninth season as head coach of the Yale football team, is more focused on creating a culture of responsibility, camaraderie, and integrity than on wins and losses but that hasnt kept the Bulldogs from finding success on the field.

On the long road to Yale College, Obed Gyedu-Larbi labored as a domestic aide and Greyhound baggage handler. He also founded a non-profit to feed and clothe homeless people in New York City. For me, he said, it was important to not only work hard for myself.

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Find out who can be a stem cell or bone marrow donor, and how to register.

A stem cell or bone marrow transplant is an important treatment for some people with types of blood cancer such as leukaemia, lymphoma and myeloma.

A transplant allows you to have high doses of chemotherapy and other treatments. The stem cellsare collected from the bloodstream or the bone marrow.Peoplehave a transplant either:

To be a donor you need to have stem cells that match the person you are donating to. To find this out, you have a blood test to look at HLA typing or tissue typing.

Staff in the laboratory look at the surface of your blood cells. They compare them to the surface of the blood cells of the person needing a transplant.

Everyone has their own set of proteins on the surface of their blood cells. The laboratory staff look for proteins called HLA markers and histocompatibility antigens. They check for 10 HLA markers. The result of this test shows how good the HLA match is between you and the person who needs the cells.

Abrother or sisteris most likely to be a match. There is a 1 in 4 chance of your cells matching.This is called a matched related donor (MRD) transplant.Anyone else in the family is unlikely to match. This can be very frustrating for relatives who are keen to help.

Sometimes if your cells are a half (50%) match, you might still be able to donate stem cells or bone marrow to a relative. This is called a haploidentical transplant.

You can't donate stem cells or bone marrow to your relative if you're not a match.

It's sometimes possible to get a match from someoneoutside of the family. This is calleda matched unrelated donor. To find a matched unrelated donor, it'susually necessary to search large numbers of people whose tissue type has been tested. So doctorssearch national and international registers to try to find a match for your relative.

Even if you can't donate to your relative, you might be ableto become a donor for someone else. You can do this by contacting one of the UK registers.

There are different donor registersin the UK.These work with each otherand with international registersto match donors with people who need stem cells. This helps doctors find donors for their patients as quickly as possiblefrom anywhere in the world.

Each registry has specific health criteriaand listmedical conditions that mightpreventyou from donating. Check their websitefor this information. Once registered, the organisation will contactyou if you are a match for someone who needs stem cells or bone marrow.

British Bone Marrow Registry (BBMR)

To register with the BBMR, you mustbe a blood donor. BBMR would like toregister those groups they are particularly short of ontheir register.This includes men between the ages of 17 and 40. And womenaged between 17 and 40 who are from Black, Asian, and minority ethnicities and mixed ethnicity backgrounds.

You have a blood test for tissue typing. Your details are kept on file until you are 60.

Anthony Nolan

You must be aged between 16 and 30 to register with Anthony Nolan. You have a cheek swab to test fortissue typing. Your details are kept on the register until you are 60.

Welsh Bone Marrow Donor Registry

You must be aged between 17 and 30 and your details are kept on the register until you are 60. You have a blood test for tissue typing.

DKMS

To register you must be aged between 17 and 55. You havea cheek swab for tissue typing. Your details stay on the register until your61st birthday.

This page is due for review. We will update this as soon as possible.

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Bone marrow is the spongy tissue inside some of the bones in the body, including the hip and thigh bones. Bone marrow contains immature cells called stem cells.

Many people with blood cancers, such as leukemia and lymphoma, sickle cell anemia, and other life threatening conditions rely on bone marrow or cord blood transplants to survive.

People need healthy bone marrow and blood cells to live. When a condition or disease affects bone marrow so that it can no longer function effectively, a marrow or cord blood transplant could be the best treatment option. For some people, it may be the only option.

This article looks at everything there is to know about bone marrow.

Bone marrow is soft, gelatinous tissue that fills the medullary cavities, or the centers of bones. The two types of bone marrow are red bone marrow, known as myeloid tissue, and yellow bone marrow, known as fatty tissue.

Both types of bone marrow are enriched with blood vessels and capillaries.

Bone marrow makes more than 220 billion new blood cells every day. Most blood cells in the body develop from cells in the bone marrow.

Bone marrow contains two types of stem cells: mesenchymal and hematopoietic.

Red bone marrow consists of a delicate, highly vascular fibrous tissue containing hematopoietic stem cells. These are blood-forming stem cells.

Yellow bone marrow contains mesenchymal stem cells, or marrow stromal cells. These produce fat, cartilage, and bone.

Stem cells are immature cells that can turn into a number of different types of cells.

Hematopoietic stem cells in the bone marrow give rise to two main types of cells: myeloid and lymphoid lineages. These include monocytes, macrophages, neutrophils, basophils, eosinophils, erythrocytes, dendritic cells, and megakaryocytes, or platelets, as well as T cells, B cells, and natural killer (NK) cells.

The different types of hematopoietic stem cells vary in their regenerative capacity and potency. They can be multipotent, oligopotent, or unipotent, depending on how many types of cells they can create.

Pluripotent hematopoietic stem cells have renewal and differentiation properties. They can reproduce another cell identical to themselves, and they can generate one or more subsets of more mature cells.

The process of developing different blood cells from these pluripotent stem cells is known as hematopoiesis. It is these stem cells that are needed in bone marrow transplants.

Stem cells constantly divide and produce new cells. Some new cells remain as stem cells, while others go through a series of maturing stages, as precursor or blast cells, before becoming formed, or mature, blood cells. Stem cells rapidly multiply to make millions of blood cells each day.

Blood cells have a limited life span. This is around 120 days for red blood cells. The body is constantly replacing them. The production of healthy stem cells is vital.

The blood vessels act as a barrier to prevent immature blood cells from leaving bone marrow.

Only mature blood cells contain the membrane proteins required to attach to and pass through the blood vessel endothelium. Hematopoietic stem cells can cross the bone marrow barrier, however. Healthcare professionals may harvest these from peripheral, or circulating, blood.

The blood-forming stem cells in red bone marrow can multiply and mature into three significant types of blood cells, each with its own job:

Once mature, these blood cells move from bone marrow into the bloodstream, where they perform important functions that keep the body alive and healthy.

Mesenchymal stem cells are present in the bone marrow cavity. They can differentiate into a number of stromal lineages, such as:

Red bone marrow produces all red blood cells and platelets and around 6070% of lymphocytes in human adults. Other lymphocytes begin life in red bone marrow and become fully formed in the lymphatic tissues, including the thymus, spleen, and lymph nodes.

Together with the liver and spleen, red bone marrow also plays a role in getting rid of old red blood cells.

Yellow bone marrow mainly acts as a store for fats. It helps provide sustenance and maintain the correct environment for the bone to function. However, under particular conditions such as with severe blood loss or during a fever yellow bone marrow may revert to red bone marrow.

Yellow bone marrow tends to be located in the central cavities of long bones and is generally surrounded by a layer of red bone marrow with long trabeculae (beam-like structures) within a sponge-like reticular framework.

Before birth but toward the end of fetal development, bone marrow first develops in the clavicle. It becomes active about 3 weeks later. Bone marrow takes over from the liver as the major hematopoietic organ at 3236 weeks gestation.

Bone marrow remains red until around the age of 7 years, as the need for new continuous blood formation is high. As the body ages, it gradually replaces the red bone marrow with yellow fat tissue. Adults have an average of about 2.6 kilograms (kg) (5.7 pounds) of bone marrow, about half of which is red.

In adults, the highest concentration of red bone marrow is in the bones of the vertebrae, hips (ilium), breastbone (sternum), ribs, and skull, as well as at the metaphyseal and epiphyseal ends of the long bones of the arm (humerus) and leg (femur and tibia).

All other cancellous, or spongy, bones and central cavities of the long bones are filled with yellow bone marrow.

Most red blood cells, platelets, and most white blood cells form in the red bone marrow. Yellow bone marrow produces fat, cartilage, and bone.

White blood cells survive from a few hours to a few days, platelets for about 10 days, and red blood cells for about 120 days. Bone marrow needs to replace these cells constantly, as each blood cell has a set life expectancy.

Certain conditions may trigger additional production of blood cells. This may happen when the oxygen content of body tissues is low, if there is loss of blood or anemia, or if the number of red blood cells decreases. If these things happen, the kidneys produce and release erythropoietin, which is a hormone that stimulates bone marrow to produce more red blood cells.

Bone marrow also produces and releases more white blood cells in response to infections and more platelets in response to bleeding. If a person experiences serious blood loss, yellow bone marrow can activate and transform into red bone marrow.

Healthy bone marrow is important for a range of systems and activities.

The circulatory system touches every organ and system in the body. It involves a number of different cells with a variety of functions. Red blood cells transport oxygen to cells and tissues, platelets travel in the blood to help clotting after injury, and white blood cells travel to sites of infection or injury.

Hemoglobin is the protein in red blood cells that gives them their color. It collects oxygen in the lungs, transports it in the red blood cells, and releases oxygen to tissues such as the heart, muscles, and brain. Hemoglobin also removes carbon dioxide (CO2), which is a waste product of respiration, and sends it back to the lungs for exhalation.

Iron is an important nutrient for human physiology. It combines with protein to make the hemoglobin in red blood cells and is essential for producing red blood cells (erythropoiesis). The body stores iron in the liver, spleen, and bone marrow. Most of the iron a person needs each day for making hemoglobin comes from the recycling of old red blood cells.

The production of red blood cells is called erythropoiesis. It takes about 7 days for a committed stem cell to mature into a fully functional red blood cell. As red blood cells age, they become less active and more fragile.

White blood cells called macrophages remove aging red cells in a process known as phagocytosis. The contents of these cells are released into the blood. The iron released in this process travels either to bone marrow for the production of new red blood cells or to the liver or other tissues for storage.

Typically, the body replaces around 1% of its total red blood cell count every day. In a healthy person, this means that the body produces around 200 billion red blood cells each day.

Bone marrow produces many types of white blood cells. These are necessary for a healthy immune system. They prevent and fight infections.

The main types of white blood cells, or leukocytes, are as follows.

Lymphocytes are produced in bone marrow. They make natural antibodies to fight infection due to viruses that enter the body through the nose, mouth, or another mucous membrane or through cuts and grazes. Specific cells recognize the presence of invaders (antigens) that enter the body and send a signal to other cells to attack them.

The number of lymphocytes increases in response to these invasions. There are two major types of lymphocytes: B and T lymphocytes.

Monocytes are produced in bone marrow. Mature monocytes have a life expectancy in the blood of only 38 hours, but when they move into the tissues, they mature into larger cells called macrophages.

Macrophages can survive in the tissues for long periods of time, where they engulf and destroy bacteria, some fungi, dead cells, and other material that is foreign to the body.

Granulocytes is the collective name given to three types of white blood cells: neutrophils, eosinophils, and basophils. The development of a granulocyte may take 2 weeks, but this time reduces when there is an increased threat, such as a bacterial infection.

Bone marrow stores a large reserve of mature granulocytes. For every granulocyte circulating in the blood, there may be 50100 cells waiting in the bone marrow to be released into the bloodstream. As a result, half the granulocytes in the bloodstream can be available to actively fight an infection in the body within 7 hours of it detecting one.

Once a granulocyte has left the blood, it does not usually return. A granulocyte may survive in the tissues for up to 45 days, depending on the conditions, but it can only survive for a few hours in circulating blood.

Neutrophils are the most common type of granulocyte. They can attack and destroy bacteria and viruses.

Eosinophils are involved in the fight against many types of parasitic infections and against the larvae of parasitic worms and other organisms. They are also involved in some allergic reactions.

Basophils are the least common of the white blood cells. They respond to various allergens that cause the release of histamines, heparin, and other substances.

Heparin is an anticoagulant. It prevents blood from clotting. Histamines are vasodilators that cause irritation and inflammation. Releasing these substances makes a pathogen more permeable and allows for white blood cells and proteins to enter the tissues to engage the pathogen.

The irritation and inflammation in tissues that allergens affect are parts of the reaction associated with hay fever, some forms of asthma, hives, and, in its most serious form, anaphylactic shock.

Bone marrow produces platelets in a process known as thrombopoiesis. Platelets are necessary for blood to coagulate and for clots to form in order to stop bleeding.

Sudden blood loss triggers platelet activity at the site of an injury or wound. Here, the platelets clump together and combine with other substances to form fibrin. Fibrin has a thread-like structure and forms an external scab or clot.

Platelet deficiency causes the body to bruise and bleed more easily. Blood may not clot well at an open wound, and there may be a higher risk of internal bleeding if the platelet count is very low.

The lymphatic system consists of lymphatic organs such as bone marrow, the tonsils, the thymus, the spleen, and lymph nodes.

All lymphocytes develop in bone marrow from immature cells called stem cells. Lymphocytes that mature in the thymus gland (behind the breastbone) are called T cells. Those that mature in bone marrow or the lymphatic organs are called B cells.

The immune system protects the body from disease. It kills unwanted microorganisms such as bacteria and viruses that may invade the body.

Small glands called lymph nodes are located throughout the body. Once lymphocytes are made in bone marrow, they travel to the lymph nodes. The lymphocytes can then travel between each node through lymphatic channels that meet at large drainage ducts that empty into a blood vessel. Lymphocytes enter the blood through these ducts.

Three major types of lymphocytes play an important part in the immune system: B lymphocytes, T lymphocytes, and NK cells.

These cells originate from hematopoietic stem cells in bone marrow in mammals.

B cells express B cell receptors on their surface. These allow the cell to attach to an antigen on the surface of an invading microbe or another antigenic agent.

For this reason, B cells are known as antigen-presenting cells, as they alert other cells of the immune system to the presence of an invading microbe.

B cells also secrete antibodies that attach to the surface of infection-causing microbes. These antibodies are Y-shaped, and each one is akin to a specialized lock into which a matching antigen key fits. Because of this, each Y-shaped antibody reacts to a different microbe, triggering a larger immune system response to fight infection.

In some circumstances, B cells erroneously identify healthy cells as being antigens that require an immune system response. This is the mechanism behind the development of autoimmune conditions such as multiple sclerosis, scleroderma, and type 1 diabetes.

These cells are so-called because they mature in the thymus, which is a small organ in the upper chest, just behind the sternum. (Some T cells mature in the tonsils.)

There are many different types of T cells, and they perform a range of functions as part of adaptive cell-mediated immunity. T cells help B cells make antibodies against invading bacteria, viruses, or other microbes.

Unlike B cells, some T cells engulf and destroy pathogens directly after binding to the antigen on the surface of the microbe.

NK T cells, not to be confused with NK cells of the innate immune system, bridge the adaptive and innate immune systems. NK T cells recognize antigens presented in a different way from many other antigens, and they can perform the functions of T helper cells and cytotoxic T cells. They can also recognize and eliminate some tumor cells.

These are a type of lymphocyte that directly attack cells that a virus has infected.

A bone marrow transplant is useful for various reasons. For example:

Stem cells mainly occur in four places:

Stem cells for transplantation are obtainable from any of these except the fetus.

Hematopoietic stem cell transplantation (HSCT) involves the intravenous (IV) infusion of stem cells collected from bone marrow, peripheral blood, or umbilical cord blood.

This is useful for reestablishing hematopoietic function in people whose bone marrow or immune system is damaged or defective.

Worldwide, more than 50,000 first HSCT procedures, 28,000 autologous transplantation procedures, and 21,000 allogeneic transplantation procedures take place every year. This is according to a 2015 report by the Worldwide Network for Blood and Marrow Transplantation.

This number continues to increase by over 7% annually. Reductions in organ damage, infection, and severe, acute graft-versus-host disease (GVHD) seem to be contributing to improved outcomes.

In a study of 854 people who survived at least 2 years after autologous HSCT for hematologic malignancy, 68.8% were still alive 10 years after transplantation.

Bone marrow transplants are the leading treatment option for conditions that threaten bone marrows ability to function, such as leukemia.

A transplant can help rebuild the bodys capacity to produce blood cells and bring their numbers to acceptable levels. Conditions that may be treatable with a bone marrow transplant include both cancerous and noncancerous diseases.

Cancerous diseases may or may not specifically involve blood cells, but cancer treatment can destroy the bodys ability to manufacture new blood cells.

A person with cancer usually undergoes chemotherapy before transplantation. This eliminates the compromised marrow.

A healthcare professional then harvests the bone marrow of a matching donor which, in many cases, is a close family member and ready it for transplant.

Types of bone marrow transplant include:

A persons tissue type is defined as the type of HLA they have on the surface of most of the cells in their body. HLA is a protein, or marker, that the body uses to help it determine whether or not the cell belongs to the body.

To check if the tissue type is compatible, doctors assess how many proteins match on the surface of the donors and recipients blood cells. There are millions of different tissue types, but some are more common than others.

Tissue type is inherited, and types pass on from each parent. This means that a relative is more likely to have a matching tissue type.

However, if it is not possible to find a suitable bone marrow donor among family members, healthcare professionals try to find someone with a compatible tissue type on the bone marrow donor register.

Healthcare professionals perform several tests before a bone marrow transplant to identify any potential problems.

These tests include:

In addition, a person needs a complete dental exam before a bone marrow transplant to reduce the risk of infection. Other precautions to lower the risk of infection are also necessary before the transplant.

Bone marrow is obtainable for examination by bone marrow biopsy and bone marrow aspiration.

Bone marrow harvesting has become a relatively routine procedure. Healthcare professionals generally aspirate it from the posterior iliac crests while the donor is under either regional or general anesthesia.

Healthcare professionals can also take it from the sternum or from the upper tibia in children, as it still contains a substantial amount of red bone marrow.

To do so, they insert a needle into the bone, usually in the hip, and withdraw some bone marrow. They then freeze and store this bone marrow.

National Marrow Donor Program (NMDP) guidelines limit the volume of removable bone marrow to 20 milliliters (ml) per kg of donor weight. A dose of 1 x 103 and 2 x 108 marrow mononuclear cells per kg is necessary to establish engraftment in autologous and allogeneic marrow transplants, respectively.

Complications related to bone marrow harvesting are rare. When they do occur, they typically involve problems related to anesthetics, infection, and bleeding.

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Bone marrow: Function, diseases, transplants, and donation

Bone Marrow Stem Cells Comments Off on Bone marrow: Function, diseases, transplants, and donation | December 23rd, 2021

Findings from a new study could point the way to new treatments for blood diseases including cancers such as leukemia and lymphoma. [3 min read]

In this schematic, cells (black spheres) within each well are committed to a specific fate, but external stimuli, such as cell-to-cell communication, can force cells out of one state and into another. (Illustration: Courtesy of Adam MacLean.)

Scientists have found a way to prove that biochemical signals sent from cell to cell play an important role in determining how those cells develop.

The study from researchers at the USC Dornsife College of Letters, Arts and Sciences was published in the journal Development on Dec. 22.

A little background:

Whats new:

We discovered that the communication process can change the formation of blood cell types dramatically, and that cells that are closer to one another have a greater influence on each others fate, MacLean said.

A controversy resolved

Researchers trying to determine what early factors nudge a cell down one developmental path or another have wondered if random fluctuations within the cell are enough to decide which path is taken. Many models have suggested they were, but recent breakthrough studies showed that random fluctuations were not enough, that something else drives cells toward their fate.

The model MacLean and Rommelfanger have developed appears to put an end to the controversy altogether. They show that cell-to-cell communication can, in fact, be the deciding factor that sets cells along a certain path.

Why it matters:

By understanding how blood cell fate decisions are made, MacLean said, we get closer to being able to identify leukemia cells of origin, and in theory we can design strategies to control or alter cell fate decision-making and stop the development of cancer.

The research could help improve cancer therapies such as bone marrow transplant.

Better understanding stem cell fate decisions, as our study provides, could provide new insight to improve clinical outcomes for these diseases, MacLean said.

More than just blood

This new model has important implications beyond the blood system.

Our model is broadly applicable, so researchers working on other cell types can apply it to find out for those other cells how important cell-to-cell communication may be, said MacLean.

Whats next:

The role of cell-to-cell communication in determining cell fate is in its nascent stages, says MacLean, but further experiments and future technologies to integrate these new types of data with sophisticated models should help expand understanding.

In addition, the team is developing methods to study the regulation of key genes involved in cell fate decisions, which should further advance their overall theoretical model.

About the study

This work was supported by National Science Foundation grant DMS 2045327 and a USC Women in Science and Engineering Top-up Fellowship.

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Communication between cells plays a major role in deciding their fate > News > USC Dornsife - USC Dornsife College of Letters, Arts and Sciences

Bone Marrow Stem Cells Comments Off on Communication between cells plays a major role in deciding their fate > News > USC Dornsife – USC Dornsife College of Letters, Arts and Sciences | December 23rd, 2021

MELVILLE, N.Y., Dec. 20, 2021 (GLOBE NEWSWIRE) -- BioRestorative Therapies, Inc. (the Company" or BioRestorative) (NASDAQ:BRTX), a life sciences company focused on adult stem cell-based therapies, today released the following year-end message.

As we reach the end of 2021, we are inspired by the many healthcare workers and biopharmaceutical companies that have worked to combat the COVID-19 pandemic. This year has been environmentally difficult, but we have seen incredible advancements in our sector which have reinforced the importance of our mission to become a clinical stage company. Since our emergence from Chapter 11 in 2020, we have sought to take positive steps at BioRestorative Therapies with the goal of making it a preeminent cell therapy company. During 2021, we achieved important transformational milestones, which created meaningful intrinsic value and advanced us toward our stated strategic goals.

In November of this year, we closed on a $23 million capital raise and concurrently listed our securities on the Nasdaq Capital Market. This is a very significant development as we are now fully funded to complete our Phase 2 trial for our lead clinical candidate, BRTX-100, for the treatment of chronic lumbar disc disease (CLDD.) During this process, we have attracted many new institutional fundamental investors as well as some retail investors. With that accomplished, I would like to briefly discuss the status of our programs and the opportunities that lie ahead of us.

BRTX-100 is our lead program for the treatment of CLDD, one of the leading causes of lower back pain. Our solution is a one-time injection of 40 million mesenchymal stem cells derived from a patients own bone marrow and expanded ex vivo before re-injection. Two things make us optimistic about this program. First, in connection with our IND filing, we referred the FDA to prior human clinical studies from different institutions that demonstrated the safety/feasibility of using mesenchymal stem cells to treat disc orders. This data not only enabled us to accelerate our clinical program and initiate a Phase 2 trial, but we believe it substantially reduces risk in offering compelling guidance on the use of cell-based interventions to treat lower back pain. Second, our manufacturing of BRTX-100 involves the use of low oxygen conditions, which ensures that the cells have enhanced survivability after introduction into the harsh avascular environment of the injured disc which has little or no blood flow. The benefits of this process are significant and are illustrated well in our recent Journal of Translational Medicine publication. Our approach is akin to transplant medicine in which specific cell types are used to replace the ones which have been lost to disease. We believe that transplanting targeted cells can offer a more attractive safety profile and potentially an improved clinical outcome. We remain optimistic that we will see significant positive clinical outcomes as we proceed with our clinical trial.

The most significant milestones we achieved in 2021 include:

Our 2022 objectives include the initiation of enrollment for our BRTX-100 clinical trial, the development of our overall product profiles via manufacturing and delivery system improvements, and the entering into of technology validation and enabling partnerships to accelerate our clinical timelines.

Some of the events and milestones that we hope to accomplish in 2022 include:

This is an exciting time to be part of the BioRestorative family. As we enter 2022 with a well-capitalized balance sheet to fully fund our Phase 2 trial, we look to accelerate our research and development pipeline. We do not take for granted that our technologies give us an opportunity to make a profound impact on the everyday lives of many people. We are grateful for the opportunity to validate such technologies; it is what we do and what we believe is the center of our core competencies.

Visit our website at http://www.biorestorative.com for more information about BioRestorative.

Thank you to the BioRestorative family for your loyalty and ongoing support.

I wish you and all those near and dear to you a wonderful Holiday Season and the very best for 2022 and beyond.

Very truly yours,

Lance AlstodtPresident, CEO and Chairman of the Board

About BioRestorative Therapies, Inc.

BioRestorative Therapies, Inc. (www.biorestorative.com) develops therapeutic products using cell and tissue protocols, primarily involving adult stem cells. Our two core programs, as described below, relate to the treatment of disc/spine disease and metabolic disorders:

Disc/Spine Program (brtxDISC): Our lead cell therapy candidate, BRTX-100, is a product formulated from autologous (or a persons own) cultured mesenchymal stem cells collected from the patients bone marrow. We intend that the product will be used for the non-surgical treatment of painful lumbosacral disc disorders or as a complementary therapeutic to a surgical procedure. The BRTX-100 production process utilizes proprietary technology and involves collecting a patients bone marrow, isolating and culturing stem cells from the bone marrow and cryopreserving the cells. In an outpatient procedure, BRTX-100 is to be injected by a physician into the patients damaged disc. The treatment is intended for patients whose pain has not been alleviated by non-invasive procedures and who potentially face the prospect of surgery. We have received authorization from the Food and Drug Administration to commence a Phase 2 clinical trial using BRTX-100 to treat chronic lower back pain arising from degenerative disc disease.

Metabolic Program (ThermoStem): We are developing a cell-based therapy candidate to target obesity and metabolic disorders using brown adipose (fat) derived stem cells to generate brown adipose tissue (BAT). BAT is intended to mimic naturally occurring brown adipose depots that regulate metabolic homeostasis in humans. Initial preclinical research indicates that increased amounts of brown fat in animals may be responsible for additional caloric burning as well as reduced glucose and lipid levels. Researchers have found that people with higher levels of brown fat may have a reduced risk for obesity and diabetes.

FORWARD-LOOKING STATEMENTS

This letter contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and such forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. You are cautioned that such statements are subject to a multitude of risks and uncertainties that could cause future circumstances, events or results to differ materially from those projected in the forward-looking statements as a result of various factors and other risks, including, without limitation, those set forth in the Company's latest Form 10-K filed with the Securities and Exchange Commission (SEC) and other filings made with the SEC. You should consider these factors in evaluating the forward-looking statements included herein, and not place undue reliance on such statements. The forward-looking statements in this letter are made as of the date hereof and the Company undertakes no obligation to update such statements.

CONTACT:

Email: ir@biorestorative.com

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BioRestorative Therapies, Inc. Releases Year-End Message - BioSpace

Bone Marrow Stem Cells Comments Off on BioRestorative Therapies, Inc. Releases Year-End Message – BioSpace | December 23rd, 2021

Dr Pradeep Mahajan, Regenerative Medicine Researcher, StemRx Bioscience Solutions highlights the importance and other aspects of stem cell technology

Globally, we are seeing a change in the type of age-specific, chronic, debilitating diseases. Thus, the manner in which we diagnose and treat such diseases is also seeing a paradigm shift. From empirical use of drugs to target-specific treatments, we are now advancing towards molecular dysfunction-based therapies.

I have been in the field of clinical medicine and surgery for over 3 decades now and I have always been fascinated by new research. Among the substantial advances in the healthcare field, I believe regenerative medicine and cell-based therapy have been game changers. We saw hematopoietic stem cells being used to treat blood cancers and related diseases for over 3-4 decades. Now we are seeing an expansion in the applications of stem cells in treating various acute, chronic, lifestyle, and even genetic and congenital diseases. The need arose because conventional medicine is gradually losing potency in treating diseases and patients are often left at the mercy of nature to take its course.

With increasing knowledge of stem cells, the trend to utilise the endogenous repair mechanisms of the human body gained popularity. Cells, growth factors and other biological products, when present at the right site; at the right moment, stimulate the natural healing mechanisms of the body and aid in management of health conditions. Cell-based therapy thus marked the beginning of a new era in regenerative medicine.

Stem cells are present in several tissues, namely, embryo, umbilical cord, placenta, as well as adult body tissues. These are the master cells of the body that have roles in development of the body, repairing and regenerating injured tissues (at a cellular level), and maintaining homeostasis even in an healthy individual. Of course, we have all heard of ethical issues regarding the use of embryonic stem cells as well as their tumor-forming issue. Regarding umbilical cord stem cells, the trend of banking this tissue has just begun; therefore, the majority of us would not have the umbilical cord as a source of stem cells. Keeping in mind these aspects, researchers started focusing on adult stem cells that can be derived from different tissues of the human body. The common sources are bone marrow, fat tissue, peripheral blood, and teeth, among others. The chief advantage is that, the source being autologous, the therapy is safe and is not associated with side effects.

Coming to the diseases that can be treated using stem cellswe have just scratched the tip of the iceberg. There are several health conditions that plague mankindarthritis, diabetes, nerve-related conditions, traumatic injuries, etc. Conventionally, one would be prescribed medications (often for prolong periods or even for their lifetime) or be advised surgery. Nonetheless, in several cases, the quality of life of a patient is compromised. The various properties of stem cells help reduce swelling in the body, regulate the immune system, enhance the functioning of other cells, and create a healthy environment for health cells to thrive. Through this, one can target a myriad of pathologies at the molecular level, in a minimally/non-invasive manner.

Patients today are quite aware of the benefits of regenerative medicine and cell based therapy, but there is still a long distance to cover. Countries are promoting research and development in the field of regenerative medicine and cell-based therapy. Research advances pertaining to introducing products with cell and scaffold based technology through tissue engineering are underway. Bioactive scaffolds that are capable of supporting activation and differentiation of host stem cells at the required site are being developed. In the future, it will be possible to use human native sites as micro-niche/micro-environment for potentiation of the human bodys site-specific response. Another breakthrough in the field of cell-based therapy is immunotherapy that aims to utilise certain parts of a persons immune system and stimulate them to fight diseases such as cancer.

The scope of cell-based therapy is endless. All we need is more research, awareness, and implementation to permit reach of the treatment to every stratum of the society. Soon, we will talk about treating diseases with cells and not pills and knives!

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Importance of stem cells-Past, present and future - Express Healthcare

Bone Marrow Stem Cells Comments Off on Importance of stem cells-Past, present and future – Express Healthcare | December 23rd, 2021

Although bone marrow mesenchymal stem cells (BMMSCs) are effective in treating chronic bacterial prostatitis (CBP), the homing of BMMSCs seems to require ultrasound induction. Dihydroartemisinin (DHA) is an important derivative of artemisinin (ART) and has been previously reported to alleviate inflammation and autoimmune diseases. But the effect of DHA on chronic prostatitis (CP) is still unclear. This study aims to clarify the efficacy and mechanism of DHA in the treatment of CBP and its effect on the accumulation of BMMSCs. The experimental CBP was produced in C57BL/6 male mice via intraurethrally administeredE. colisolution. Results showed that DHA treatment concentration-dependently promoted the accumulation of BMMSCs in prostate tissue of CBP mice. In addition, DHA and BMMSCs cotreatment significantly alleviated inflammation and improved prostate damage by decreasing the expression of proinflammatory factors such as TNF-, IL-1, and chemokines CXCL2, CXCL9, CXCL10, and CXCL11 in prostate tissue of CBP mice. Moreover, DHA and BMMSCs cotreatment displayed antioxidation property by increasing the production of glutathione peroxidase (GSH-Px), SOD, and decreasing malondialdehyde (MDA) expression. Mechanically, DHA and BMMSCs cotreatment significantly inhibited the expression of

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Dihydroartemisinin Promoted Bone Marrow Mesenchymal Stem Cell Homing and Suppressed Inflammation and Oxidative Stress against Prostate Injury in...

Bone Marrow Stem Cells Comments Off on Dihydroartemisinin Promoted Bone Marrow Mesenchymal Stem Cell Homing and Suppressed Inflammation and Oxidative Stress against Prostate Injury in… | December 23rd, 2021

Abstract: Hematopoietic stem cell transplantation (HSCT) is an effective treatment method used in many neoplastic and non-neoplastic diseases that affect the bone marrow, blood cells, and immune system.The procedure is associated with a risk of adverse events, mostly elated to the immune response after transplantation. The aim of our research was to identify genes, processes and cellular entities involved in the variety of changes occurring after allogeneic HSCT in children by performing a whole genome expression assessment together with pathway enrichment analysis. We conducted a prospective study of 27 patients (aged 1.518 years) qualified for allogenic HSCT. Blood samples were obtained before HSCT and 6 months after the procedure. Microarrays were used to analyze gene expressions in peripheral blood mononuclear cells. This was followed by Gene Ontology (GO) functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrich- ment analysis, and proteinprotein interaction (PPI) analysis using bioinformatic tools. We found 139 differentially expressed genes (DEGs) of which 91 were upregulated and 48 were downregulated. Blood microparticle, extracellular exosome, B-cell receptor signaling pathway, complement activation and antigen binding were among GO terms found to be significantly enriched. The PPI analysis identified 16 hub genes. Our results provide insight into a broad spectrum of epigenetic changes that occur after HSCT. In particular, they further highlight the importance of extracellular vesicles (exosomes and microparticles) in the post-HSCT immune response.

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Analysis of Peripheral Blood Mononuclear Cells Gene Expression Highlights the Role of Extracellular Vesicles in the Immune Response following...

Bone Marrow Stem Cells Comments Off on Analysis of Peripheral Blood Mononuclear Cells Gene Expression Highlights the Role of Extracellular Vesicles in the Immune Response following… | December 23rd, 2021

DUARTE, Calif.--(BUSINESS WIRE)--City of Hope doctors presented data on an investigational bispecific antibody for multiple myeloma and the CMVPepVax, a City of Hope-developed vaccine against the cytomegalovirus, at this years ASH Annual Meeting.

City of Hope continues to be a leader in innovative research on investigational immunotherapies for blood cancers and improving stem cell transplants, said Eileen Smith, M.D., City of Hopes Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation. New research at this years ASH conference includes promising investigational immunotherapies for lymphoma, multiple myeloma, leukemia and other blood cancers and an update on a City of Hope-developed vaccine to prevent a virus that can cause serious complications in stem cell transplant recipients.

Here are highlights of City of Hope research presented at the ASH conference:

Investigational bispecific antibody for multiple myeloma is well-tolerated and effective

Bispecific antibodies are an emerging immunotherapy against blood cancers. City of Hopes Elizabeth Budde, M.D., Ph.D., presented at this years ASH conference on mosunetuzumab. The research demonstrated that mosunetuzumab is a safe and effective investigational bispecific antibody for follicular lymphoma.

Talquetamab is an investigational therapy that is also demonstrating encouraging results for the treatment of relapsed multiple myeloma, according to a study led by Amrita Krishnan, M.D., director of the Judy and Bernard Briskin Center for Multiple Myeloma Research at City of Hope and chief, Division of Multiple Myeloma.

Talquetamab targets the G protein-coupled receptor family C group 5 member (GPRC5D) that has a high expression on malignant plasma cells and is limited on normal human tissue. The first-in-class bispecific antibody directs T cells to kill multiple myeloma cells by binding to both GPRC5D and CD3 receptors.

Patients with relapsed or difficult to treat multiple myeloma in the Phase 1 study received recommended Phase 2 doses as an injection on a weekly or biweekly basis. By increasing the doses slowly, researchers hope that will help to minimize the severity of cytokine release syndrome.

Krishnan presented data on 55 patients. For the study, 30 patients who received the therapy weekly (and their results were evaluable, meaning they could be included in the study) and 23 people who received it on a biweekly schedule were included. The study is ongoing.

In the weekly cohort, the overall response rate was 70% and there was a very good partial response or better in 57% of patients.

The response numbers are very strong and whats also remarkable is that the responses were durable and deepened over time in both groups, Krishnan said.

Cytokine release syndrome occurred in 73% of the weekly dose cohort, but only one patient had a severe case and it was treatable. Other side effects included neutropenia and dysgeusia.

We are excited that our results demonstrated that talquetamab is well-tolerated and highly effective at the Phase 2 dose level and with tolerable side effects, Krishnan said.

Further studies of the therapy on its own or in combination with other treatments for multiple myeloma are underway.

City of Hope-developed vaccine to prevent cytomegalovirus shows safety, tolerability

Despite therapies to help prevent the cytomegalovirus (CMV), which can flare up in blood marrow/stem cell transplant recipients who are immunocompromised, CMV infections are one of the most common complications in these patients. Furthermore, the antiviral drugs used to prevent flare-ups are toxic, expensive and increase the risk of other opportunistic infections.

City of Hope has developed an anti-CMV vaccine, known as CMVPepVax. At this years ASH conference, the results of a Phase 2 trial using CMVPepVax were reported by Ryotaro Nakamura, M.D., City of Hopes Jan & Mace Siegel Professor in Hematology & Hematopoietic Cell Transplantation in the Division of Leukemia.

The double blinded, placebo-controlled, randomized Phase 2 trial enrolled stem cell transplant recipients from four transplant centers, including City of Hope. Nakamura reported on data from 32 patients in the vaccine arm and 29 patients in the placebo arm.

CMVPepVax was delivered via injections 28 days after transplant and 56 days after the procedure.

Trial results demonstrated that there was no difference in CMV reactivation in both arms.

CMVPepVax was well-tolerated in patients with no increase in adverse side effects. Transplant outcomes were also similar between the two groups when comparing one-year overall survival, relapse-free survival, nonrelapse mortality, relapse and acute graft-versus-host disease (GVHD).

Significantly higher levels of CMV-targeting T cells were measured in patients in the vaccine arm who did not have CMV in their bloodstream. In patients who had the CMVPepVax injections, robust expansion of functional T cells also occurred.

Our results confirm that CMVPepVax is safe to use and provides an immune response, Nakamura said. Although the vaccine did not reduce the presence of CMV in the bloodstream, there were favorable CD8 T cell responses, which are protective in principle, but maybe didn't recover fast enough to prevent CMV from reactivating.

Next steps include researching whether stem cell donors who receive the vaccine can transfer immunity to patients, as well as providing a booster to patients. This may lead to faster immune responses after transplant.

Using probiotics for stem cell transplant patients

City of Hope is a leader in bone marrow and stem cell transplantation it was one of the first cancer centers nationwide to perform a bone marrow transplant and has performed more than 17,000 bone marrow/stem cell transplants since 1976. Because of this leadership, City of Hope doctors and scientists are investigating how to make the transplant process better, as well as how to deal with complications that may arise from the procedure, such as GVHD.

Led by Karamjeet S. Sandhu, M.D., an assistant professor in City of Hope's Division of Leukemia in the Department of Hematology & Hematopoietic Cell Transplantation, a City of Hope study examined how adding the probiotic CBM 588 to transplant recipients diets might decrease inflammation in the gut and lower the risk of GVHD. The results were discussed in an oral presentation at the ASH conference.

Sandhu explained that the body hosts microbial communities, known as the microbiome. These microbes help the body in several metabolic processes, such as digesting food, strengthening the immune system, protecting against other bacteria and producing vitamins, including B vitamins.

Recent studies have shown the microbiome can play a role in cancer risk and how a persons body responds to cancer treatment. In people with blood cancers who receive a transplant, there is a direct link between the health of microbiome and survival.

Imbalance among these microbial species have also been associated with several transplant complications including GVHD, said Sandhu, M.D. He added that the imbalance also contributes to morbidity and mortality.

For the study, Sandhu and his team used Clostridium Butyricum Miyairi 588 (CBM588), a probiotic strain that has been used in Japan for several decades to manage diarrhea caused by antibiotics or infections. CBM588 is a butyrate-producing bacteria present in the spore form in soil and food. Administration of CBM588 has shown anti-inflammatory and immune modulating effects, as well as evidence of anti-cancer activity.

This was the first study of CBM588 among bone marrow/stem cell transplant recipients. Fifteen patients received the current standard of care therapies to prevent GVHD and 21 received CBM588 in addition to standard of care for GVHD.

Our study demonstrated that CMB588 is safe and feasible to use in this patient population without increasing mortality, Sandhu said. We even noted an improvement in gastrointestinal GVHD, but further studies are needed to prove the effect and mechanism of action among recipients of bone marrow/stem cell transplantation.

Joint study examines somatic mutations in CMML patients, impact on stem cell transplants

Chronic myelomonocytic leukemia (CMML) is a rare form of leukemia that primarily affects older adults. The only potential cure at this time is allogeneic hematopoietic cell transplantation, also known as a stem cell transplant.

Research has shown that somatic mutations genetic changes that are acquired during life and not inherited are an important factor in determining prognosis for CMML patients. However, limited data are available regarding their impact on outcomes after CMML patients receive transplant.

A joint study between City of Hope and Center for International Blood and Marrow Transplant Research (CIBMTR) analyzed the relationship between somatic mutations in CMML and their impact on stem cell transplants.

Additionally, the study aimed to evaluate two separate scoring systems commonly used in nontransplant CMML patients, the CMML-specific prognostic scoring system (CPSS) and molecular CPSS (CPSS-Mol), which takes into account the somatic mutations, to find out if they can predict the results of a transplant.

Led by City of Hopes Matthew Mei, M.D., an associate professor in City of Hopes Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, the study included 313 patients across 78 different transplant centers, all of whom underwent a comprehensive mutation analysis of 131 genes performed at City of Hope under the supervision of Raju K. Pillai, M.D., director of Pathology Core Laboratories in Beckman Research Institute of City of Hope.

The study found that 93% of patients had at least one mutation identified, and the median number of mutations was three. The most frequently mutated genes were ASXL1 (62%), TET2 (35%), KRAS/NRAS (33% combined) and SRSF2 (31%); TP53 was mutated in 3% of patients.

Both the CPSS and CPSS-Mol were predictive of overall survival after transplant; however, neither system was able to identify patients who were at an increased risk of relapse. Furthermore, the incorporation of somatic mutations did not appear to refine the prognosis.

Our study is the largest analysis of CMML patients who underwent a stem cell transplant with paired mutation analysis, Mei said. Overall, patients with CMML remain at high risk for relapse after transplant. Novel therapies aimed at decreasing relapse and making transplants safer, as well as improved methods of predicting outcomes of transplant in CMML, are still critically needed.

Additional research on chimeric antigen receptor (CAR) T therapy and stem cell transplantation presented at ASH

Tanya Siddiqi, M.D., director of City of Hope's Chronic Lymphocytic Leukemia Program, also presented a poster on the Transcend NHL 001 trial at the ASH conference, and Ibrahim Aldoss, M.D., associate professor, City of Hope's Division of Leukemia, presented a poster on the outcomes of allogeneic hematopoietic cell transplantation in adults with Ph-like acute lymphoblastic leukemia.

City of Hope is a leader in blood cancer research and treatment. The National Cancer Institute-designated comprehensive cancer center has performed more than 17,000 bone marrow/stem cell transplants and is a leader in chimeric antigen receptor (CAR) T therapy, with nearly 800 patients treated with immune effector cells, including CAR T therapy, and nearly 80 open or completed trials.

About City of Hope

City of Hope is an independent biomedical research and treatment center for cancer, diabetes and other life-threatening diseases. Founded in 1913, City of Hope is a leader in bone marrow transplantation and immunotherapy such as CAR T cell therapy. City of Hopes translational research and personalized treatment protocols advance care throughout the world. Human synthetic insulin, monoclonal antibodies and numerous breakthrough cancer drugs are based on technology developed at the institution. A National Cancer Institute-designated comprehensive cancer center and a founding member of the National Comprehensive Cancer Network, City of Hope is ranked among the nations Best Hospitals in cancer by U.S. News & World Report. Its main campus is located near Los Angeles, with additional locations throughout Southern California and in Arizona. Translational Genomics Research Institute (TGen) became a part of City of Hope in 2016. AccessHope, a subsidiary launched in 2019, serves employers and their health care partners by providing access to NCI-designated cancer center expertise. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.

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City of Hope presents leading-edge research on blood cancer therapies and its vaccine to reduce stem cell transplant complications at American Society...

Bone Marrow Stem Cells Comments Off on City of Hope presents leading-edge research on blood cancer therapies and its vaccine to reduce stem cell transplant complications at American Society… | December 23rd, 2021

Mysuru

An 88-year-old gentleman presented to Manipal Hospital Mysore with blackish discoloration of the heel of left foot. He was diabetic & was on regular treatment for the same. For the current problem, he had already received several medications including intra venous antibiotics with little improvement. Upon examination he was detected to have Critical Limb Ischemia (CLI) with gangrene of heel of left foot. Large number of such patients end up with amputation of leg. Our aim in such situation is to first try to save the limb. Amputation should be the last resort when everything else fails. Said Dr. Upendra Shenoy Cardiothoracic and Vascular Surgeon Manipal Hospital Mysore, while giving details about the patient. While addressing the media Dr. C B Keshavamurthy Consultant Interventional Cardiology, Manipal Hospital Mysore said, Patients angiogram showed diffuse disease in all blood vessels of the leg with critical blocks in many areas.

We performed angioplasty on the limb. The procedure improved the blood supply to the limb, but additional treatment was required to restore blood circulation to the foot and toes. Dr. Shenoy and team decided to implement stem cell therapy, hybrid procedure of peripheral angioplasty with stem cell injection. First of its kind procedure in Mysore. Stem cell therapy involves the injection of stem cells obtained from the bone marrow of healthy individuals.

These stem cells can transform themselves into different tissues according to the requirement. In this case, the stem cells stimulate the formation of new blood vessels, said Dr Upendra Shenoy while explaining about the therapy. Dr Shenoy further added, On the day after angioplasty, we injected the stem cell into the calf muscles of the patient.

The dose depends upon the weight of the patient. If the weight is below 60 kg, the doctor injects about 150 million stem cells. In patients with more than 60 kg, the dose is about 200 million.

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Stem cell therapy holds immense promise for the treatment of patients with non-healing ischemic leg wounds - Ibcworldnews

Bone Marrow Stem Cells Comments Off on Stem cell therapy holds immense promise for the treatment of patients with non-healing ischemic leg wounds – Ibcworldnews | December 23rd, 2021

Advance Market Analytics published a new research publication on Stem Cells Market Insights, to 2026 with 232 pages and enriched with self-explained Tables and charts in presentable format. In the Study you will find new evolving Trends, Drivers, Restraints, Opportunities generated by targeting market associated stakeholders. The growth of the Stem Cells Market was mainly driven by the increasing R&D spending across the world.

Some of the key players profiled in the study are:

Smith & Nephew (United Kingdom),Celgene Corporation (United States),BIOTIME, INC. (United States),Cynata (Australia),Applied Cell Technology (Hungary),STEMCELL Technologies Inc. (Canada),BioTime Inc. (United States),Cytori Therapeutics, Inc. (United States),Astellas Pharma Inc. (Japan),U.S. Stem Cell, Inc. (United States),Takara Holdings. (Japan)

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Scope of the Report of Stem Cells

The stem cell is used for treating chronic diseases such as cardiovascular disorders, cancer, diabetes, and others. Growing research and development in stem cell isolation techniques propelling market growth. For instance, a surgeon from Turkey developed a method for obtaining stem cells from the human body without enzymes which are generally used for the isolation of stem cells. Further, growing healthcare infrastructure in the developing economies and government spending on the life science research and development expected to drive the demand for stem cell market over the forecasted period.

Market Trend:

Emphasizing On Development of Regenerative Medicine

Technological Advancement in Stem Cell Harvesting and Isolation Techniques

Market Drivers:

Rising Prevalence of Chronic Diseases such as Cardiovascular Disorders, Cancer, and others

Growing Healthcare Infrastructure in the Developing Economies

Challenges:

Lack of Awareness Regarding Stem Cell Therapy in the Low and Middle Income Group Countries

Opportunities:

Growing Demand for Cellular Therapies

Rising Application of Autologous Therapy

The titled segments and sub-section of the market are illuminated below:by Type (Adult Stem Cells (Neuronal, Hematopoietic, Mesenchymal, Umbilical Cord, Others), Human Embryonic Stem Cells (hESC), Induced Pluripotent Stem Cells, Very Small Embryonic-Like Stem Cells), Application (Regenerative Medicine (Neurology, Orthopedics, Oncology, Hematology, Cardiovascular and Myocardial Infraction, Injuries, Diabetes, Liver Disorder, Incontinence, Others), Drug Discovery and Development), Technology (Cell Acquisition (Bone Marrow Harvest, Umbilical Blood Cord, Apheresis), Cell Production (Therapeutic Cloning, In-vitro Fertilization, Cell Culture, Isolation), Cryopreservation, Expansion and Sub-Culture), Therapy (Autologous, Allogeneic)

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Region Included are: North America, Europe, Asia Pacific, Oceania, South America, Middle East & Africa

Country Level Break-Up: United States, Canada, Mexico, Brazil, Argentina, Colombia, Chile, South Africa, Nigeria, Tunisia, Morocco, Germany, United Kingdom (UK), the Netherlands, Spain, Italy, Belgium, Austria, Turkey, Russia, France, Poland, Israel, United Arab Emirates, Qatar, Saudi Arabia, China, Japan, Taiwan, South Korea, Singapore, India, Australia and New Zealand etc.

Strategic Points Covered in Table of Content of Global Stem Cells Market:

Chapter 1: Introduction, market driving force product Objective of Study and Research Scope the Stem Cells market

Chapter 2: Exclusive Summary the basic information of the Stem Cells Market.

Chapter 3: Displaying the Market Dynamics- Drivers, Trends and Challenges of the Stem Cells

Chapter 4: Presenting the Stem Cells Market Factor Analysis Porters Five Forces, Supply/Value Chain, PESTEL analysis, Market Entropy, Patent/Trademark Analysis.

Chapter 5: Displaying market size by Type, End User and Region 2015-2020

Chapter 6: Evaluating the leading manufacturers of the Stem Cells market which consists of its Competitive Landscape, Peer Group Analysis, BCG Matrix & Company Profile

Chapter 7: To evaluate the market by segments, by countries and by manufacturers with revenue share and sales by key countries (2021-2026).

Chapter 8 & 9: Displaying the Appendix, Methodology and Data Source

Finally, Stem Cells Market is a valuable source of guidance for individuals and companies in decision framework.

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Stem Cells Market to Witness Gigantic Growth by 2026 LSMedia - LSMedia

Bone Marrow Stem Cells Comments Off on Stem Cells Market to Witness Gigantic Growth by 2026 LSMedia – LSMedia | December 23rd, 2021

PALM BEACH, Fla., Dec. 21, 2021 /PRNewswire/ -- FinancialNewsMedia.com News Commentary - Systemic mastocytosis is rare disease which affects very few people and it causes due to C-kit mutation which leads to higher number of mast cell production in the body resulting in accumulation of excessive mast cells in the internal body organs such as spleen, liver, bone marrow and small intestine etc. Recently, the World Health Organization (WHO) updated the prognosis, diagnosis and systemic mastocytosis treatment guidelines for the disease which in turn helped to bring uniformity in the approach by healthcare professionals. The manufacturers in the systemic mastocytosis treatment market are focusing on evaluating possible treatment options to cure the disease by investing heavily in the research & development. Various leading manufacturers are focusing on gaining FDA approval to respective drugs for the systemic mastocytosis treatment to enhance their revenue generation. A reportfrom Future Market Insights said:"Increasing awareness about the systemic mastocytosis treatment as well as symptoms of the disease due to extended effort by non-profit organizations, governmental associations and through other platforms expected to drive the growth of the systemic mastocytosis treatment market Increasing approvals and launches of drugs for the systemic mastocytosis treatment expected to drive the growth of the market Increasing spending on research & development by various pharmaceutical companies to develop novel systemic mastocytosis treatment expected to further fuel the growth of market. Increasing early diagnosis rate subsequently followed by increasing treatment seeking rate further expected to drive the growth of the systemic mastocytosis treatment market." Active companies in the markets today include: Hoth Therapeutics, Inc. (NASDAQ:HOTH), Longeveron Inc. (NASDAQ: LGVN), Bristol Myers Squibb (NYSE: BMY), Takeda Pharmaceutical Company Limited (NYSE: TAK), Amgen (NASDAQ: AMGN).

Future Market Insights continued:"The global systemic mastocytosis treatment market is expected to experience significant growth due to increasing novel treatment options. By drug class, systemic mastocytosis treatment market is expected to be dominated by the mast cell stabilizers due to superior efficacy. By indication, systemic mastocytosis treatment market is expected to be dominated by indolent systemic mastocytosis (ISM) due to higher prevalence. By route o administration, systemic mastocytosis treatment market is expected to be dominated by injectables. By distribution channel, systemic mastocytosis treatment market is expected to be dominated by the retail pharmacies due to higher patient footfall. The global systemic mastocytosis treatment market is expected to be dominated by the North America due to comparatively higher prevalence of the disease. Europe systemic mastocytosis treatment market is expected to be second most lucrative market due to higher treatment seeking rate. Latin America expected to show gradual growth in the systemic mastocytosis treatment market due to steadily increasing diagnosis. Asia-Pacific is emerging systemic mastocytosis treatment market due to increasing diagnosis subsequently followed by treatment. Middle East & Africa is the least lucrative systemic mastocytosis treatment market due to least diagnostic rate and lower awareness about the symptoms."

Hoth Therapeutics, Inc. (NASDAQ:HOTH) BREAKING NEWS: Hoth Therapeutics Announces Submission of Orphan Designation Application for HT-KIT to Treat Mastocytosis Hoth Therapeutics, Inc., a patient-focusedclinical-stage biopharmaceutical company, announced it submitted an Orphan Drug Designation Application to the US Food and Drug Administration (FDA) for HT-KIT for the treatment of mastocyctosis. HT-KIT is an antisense oligonucleotide that targets the proto-oncogene cKIT by inducing mRNA frame shifting, resulting in apoptosis of neoplastic mast cells. The KIT signaling pathway is implicated in multiple diseases, including all types of mastocytosis (such as aggressive systemic mastocytosis (ASM), mast cell leukemia (MCL), and systemic mastocytosis with associated hematological neoplasm (SM-AHN)), acute myeloid leukemia, gastrointestinal stromal tumors, and anaphylaxis.

Drugs intended to treat orphan diseases (rare diseases that affect less than 200,000 people in the US)are eligible to apply for Orphan Drug Designation (ODD), which provides multiple benefits to the sponsor during development and after approval. Hoth intends to pursue these benefits as part of the drug development for HT-KIT for treatment of mastocytosis, pending designation of the ODD application.

Benefits of Orphan Drug Designation - Under the Orphan Drug Act, drug companies can apply for ODD, and if granted, the drug will have a status which gives companies exclusive marketing and development rights along with other benefits to recover the costs of researching and developing the drug. A tax credit of 50% of the qualified clinical drug testing costs awarded upon drug approval is also possible. Regulatory streamlining and provide special assistance to companies that develop drugs for rare patient populations. In addition to exclusive rights and cost benefits, the FDA will provide protocol assistance, potential decreased wait-time for drug approval, discounts on registration fees, and eligibility for market exclusivity after approval.

Key benefits of ODD:

Hoth recently announcedthat its novelanti-cancer therapeuticexhibited highly positive results in humanized mast cell neoplasm models, representative in vitro and in vivo models for aggressive, mast cell-derived cancers such as mast cell leukemia and mast cell sarcoma. CONTINUED Read the Hoth Therapeutics full press release by going to: https://ir.hoththerapeutics.com/news-releases

In other news and developments of note in the markets this week:

Amgen (NASDAQ: AMGN) recently announced that the U.S. Food and Drug Administration (FDA) has approved Amgen and AstraZeneca'sTezspire (tezepelumab-ekko) for the add-on maintenance treatment of adult and pediatric patients aged 12 years and older with severe asthma.

Tezspirewas approved following a Priority Review by the FDA and based on results from the PATHFINDER clinical trial program. The application included results from the pivotal NAVIGATOR Phase 3 trial in whichTezspiredemonstrated superiority across every primary and key secondary endpoint in patients with severe asthma, compared to placebo, when added to standard therapy.

Longeveron Inc. (NASDAQ: LGVN), a clinical stage biotechnology company developing cellular therapies for chronic aging-related and certain life-threatening conditions, recently announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) for Lomecel-B for the treatment of Hypoplastic Left Heart Syndrome (HLHS), a rare and life-threatening congenital heart defect in infants.

ODD is intended to assist and encourage companies to develop safe and effective therapies for the treatment of rare diseases or conditions. ODD positions Longeveron to be able to potentially leverage a range of financial and regulatory benefits, including government grants for conducting clinical trials, waiver of FDA user fees for the potential submission of a marketing application, and certain tax credits. Receiving ODD may also result in the product receiving seven years market exclusivity upon approval for use in the rare disease or condition for which the product was designated if all of the statutory and regulatory requirements are met.

Bristol Myers Squibb (NYSE: BMY) recently announced thatOrencia(abatacept) was approved by the U.S. Food and Drug Administration (FDA) for the prophylaxis, or prevention, of acute graft versus host disease (aGvHD), in combination with a calcineurin inhibitor (CNI) and methotrexate (MTX), in adults and pediatric patients 2 years of age and older undergoing hematopoietic stem cell transplantation (HSCT) from a matched or 1 allele-mismatched unrelated donor (URD).

"Orenciais the first FDA-approved therapy to prevent acute graft versus host disease following hematopoietic stem cell transplant, a potentially life-threatening complication that can pose a comparatively higher risk to racial and ethnic minority populations in the U.S. due to difficulty finding appropriately matched donors," said Tina Deignan, senior vice president, U.S. Immunology, Bristol Myers Squibb. "With this fourth indication forOrencia,Bristol Myers Squibb draws on its legacy and expertise in both immunology and hematology to deliver an important treatment option for patients in a disease with high unmet need.

Takeda Pharmaceutical Company Limited (NYSE: TAK) announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended the approval of intravenous (IV) vedolizumab for the treatment of adult patients with moderately to severely active chronic pouchitis, who have undergone proctocolectomy and ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC), and have had an inadequate response with or lost response to antibiotic therapy. The CHMP opinion will now be reviewed by the European Commission. If approved, vedolizumab will become the first treatment indicated for active chronic pouchitis across the European Union.

DISCLAIMER: FN Media Group LLC (FNM), which owns and operates Financialnewsmedia.com and MarketNewsUpdates.com, is a third- party publisher and news dissemination service provider, which disseminates electronic information through multiple online media channels. FNM is NOT affiliated in any manner with any company mentioned herein. FNM and its affiliated companies are a news dissemination solutions provider and are NOT a registered broker/dealer/analyst/adviser, holds no investment licenses and may NOT sell, offer to sell or offer to buy any security. FNM's market updates, news alerts and corporate profiles are NOT a solicitation or recommendation to buy, sell or hold securities. The material in this release is intended to be strictly informational and is NEVER to be construed or interpreted as research material. All readers are strongly urged to perform research and due diligence on their own and consult a licensed financial professional before considering any level of investing in stocks. All material included herein is republished content and details which were previously disseminated by the companies mentioned in this release. FNM is not liable for any investment decisions by its readers or subscribers. Investors are cautioned that they may lose all or a portion of their investment when investing in stocks. For current services performed FNM was compensated twenty five hundred dollars for news coverage of current press release issued by: Hoth Therapeutics, Inc. by a non-affiliated third party.

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Systemic Mastocytosis Treatments Gain Hope Due To Increasing Novel Treatment Options - PRNewswire

Bone Marrow Stem Cells Comments Off on Systemic Mastocytosis Treatments Gain Hope Due To Increasing Novel Treatment Options – PRNewswire | December 23rd, 2021

Successful stem cell therapies are no science fiction anymore

Stem cells from the umbilical cord are special. They are young, potent, and viable. Numerous clinical studies are being conducted worldwide researching the suitability of stem cells for the regeneration of damaged tissues after accidents, degenerative diseases like e.g. slipped intervertebral discs, or cancer treatment. Like Vita 34, many health professionals and scientists believe in the potential of stem cells: Umbilical cord blood and tissue that is rich in stem cells will be an important therapeutic option in future medicine.

Stem cell therapies give hope to many patients and are an important therapeutic option.

Vita 34 actively participates in this development. We are involved with our in-house department of research and development and in collaboration with leading universities and research institutions all over Europe in basic and application research. Vita 34-customers benefit from this knowhow: The expanding knowledge in stem cell research makes your childs stem cell deposits more valuable every day.

Applications of stem cells in modern medicine

Stem cells have been applied in the treatment of serious diseases for more than 55 years. They are applied especially to treat cancers, which require high-dose chemotherapy within the scope of medical care. The patients own stem cells are extracted from bone marrow or peripheral blood prior to high-dose chemotherapy, stored temporarily and transplanted after the treatment in order to minimize the side effects of the aggressive chemotherapy and to support the regeneration of destroyed cells.

Applications of stem cells in modern medicine

Stem cells have been applied in the treatment of serious diseases for more than 55 years. They are applied especially to treat cancers, which require high-dose chemotherapy within the scope of medical care. The patients own stem cells are extracted from bone marrow or peripheral blood prior to high-dose chemotherapy, stored temporarily and transplanted after the treatment in order to minimize the side effects of the aggressive chemotherapy and to support the regeneration of destroyed cells.

Besides cancer, several 100,000 people come down with common diseases like dementia, which belongs to the neurodegenerative diseases, cardiac infarction, stroke, arthritis, or diabetes every year. The lifelong therapy causes enormous costs in the health care system. Stem cell therapy offers great potential for the treatment of such diseases. Experts expect that every seventh person up to the age of 70 will need a therapy based on stem cells in the future to regenerate sick or aged cells and tissues.

To be able to store stem cells does not automatically mean to apply stem cells. The transplantation of stem cells requires enormous knowledge and experience. So far, 51 stem cell deposits stored with Vita 34 have been applied in practice. They were already applied in the treatment of cancers (like leukemia and neuroblastoma), hematopoietic disorders (like aplastic anemia or beta thalassemia), immune defects (like SCID or Wiskott Aldrich syndrome), infantile brain damage, and infantile diabetes type 1.

"Stem cells are called the building blocks of life, because an entire human being develops from the very first stem cell. The potential of stem cells therefore is enormous and already provides for entirely new therapeutic options in the field of individualized, regenerative medicine.

By the way, as measured by applications in clinical treatment attempts and studies, Vita 34 is the most experienced private stem cell bank in Europe.

Scientists expect further findings and developments in the field of stem cell therapy in the next years.

Areas of application of stem cells.

Stem cells have already been applied successfully for:

In clinical studies and treatment attempts, stem cell therapies are tested with the following indications:

More about the topic

Is each stem cell like the other? No, experts know different types of stem cells. Embryonic stem cells differ in their properties from adult stem cells, and omnipotent stem cells can do more than unipotent stem cells. And what is the difference again between mesenchymal stem cells and hematopoietic stem cells? Read the overview to learn all that.

Stem cells age with us and can suffer damages from diseases and environmental influences. Stem cells from the umbilical cord are different. They are extracted safely and easily right after birth and frozen by means of cryo-preservation. They do not age and remain untroubled by environmental influences and diseases.

Umbilical cord blood is much too good to throw away. That is why many parents want to store their offsprings umbilical cord blood for the future. They are often faced with the question, whether to donate their childs stem cells publicly or store them privately to take individual precautions. Vita 34 offers parents the option VitaPlusDonation to combine both possibilities.

As a precaution, store either the umbilical cord blood or the umbilical cord tissue after the birth of your child. We offer both at different prices and terms. Also a financing is possible. Optionally, you can also donate the umbilical cord blood.

Storing cord blood and cord tissue

Our guidebook for parents contains comprehensive information on the subject of cord blood storage. Order the guidebook by mail at no charge and without any obligation.

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Application of stem cells Vita 34

Cardiac Stem Cells Comments Off on Application of stem cells Vita 34 | December 23rd, 2021

Stem cells are special human cells that can develop into many different types of cells, from muscle cells to brain cells.

Stem cells also have the ability to repair the damaged cells.These cells have strong healing power. They can evolve into any types of cell.

Researches are going on and it is believed that stem cell therapies can cure ailments like paralysis and Alzheimers as well. Let us have a detailed look at stem cells, its types and functions.

Also Read: Gene Therapy

Stem cells are of the following different types:

The fertilized egg begins to divide immediately. All the cells in the young embryo are totipotent cells. These cells form a hollow structure within a few days. Cells in one region group together to form the inner cell mass. This contains pluripotent cells that make up the developing foetus.

The embryonic stem cells can be further classified as:

These stem cells are obtained from developed organs and tissues. They can repair and replace the damaged tissues in the region where they are located. For eg., hematopoietic stem cells are found in the bone marrow. These stem cells are used in bone marrow transplants to treat specific types of cancers.

These cells have been tested and arranged by converting tissue-specific cells into embryonic cells in the lab. These cells are accepted as an important tool to learn about normal development, onset and progression of the disease and also helpful in testing various drugs. These stem cells share the same characteristics as embryonic cells do. They also have the potential to give rise to all the different types of cells in the human body.

These cells are mainly formed from the connective tissues surrounding other tissues and organs known as the stroma. These mesenchymal stem cells are accurately called stromal cells. The first mesenchymal stem cells were found in the bone marrow that is capable of developing bones, fat cells, and cartilage.

There are different mesenchymal stem cells that are used to treat various diseases as they have been developed from different tissues of the human body. The characteristics of mesenchymal stem cells depend on the organ from where they originate.

Following are the important applications of stem cells:

This is the most important application of stem cells. The stem cells can be used to grow a specific type of tissue or organ. This can be helpful in kidney and liver transplants. The doctors have already used the stem cells from beneath the epidermis to develop skin tissue that can repair severe burns or other injuries by tissue grafting.

A team of researchers have developed blood vessels in mice using human stem cells. Within two weeks of implantation, the blood vessels formed their network and were as efficient as the natural vessels.

Stem cells can also treat diseases such as Parkinsons disease and Alzheimers. These can help to replenish the damaged brain cells. The researchers have tried to differentiate embryonic stem cells into these type of cells and make it possible to treat diseases.

The adult hematopoietic stem cells are used to treat cancers, sickle cell anaemia, and other immunodeficiency diseases. These stem cells can be used to produce red blood cells and white blood cells in the body.

Stem Cells originate from different parts of the body. Adult stem cells can be found in specific tissues in the human body. Matured cells are specialized to conduct various functions. Generally, these cells can develop the kind of cells found in tissues where they reside.

Embryonic Stem Cells are derived from 5-day old blastocysts that develop into embryos and are pluripotent in nature. These cells can develop any type of cell and tissue in the body. These cells have the potential to regenerate all the cells and tissues that have been lost because of any kind of injury or disease.

To know more about stem cells, its types, applications and sources, keep visiting BYJUS website.

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What are Stem Cells? - Types, Applications and Sources

Cardiac Stem Cells Comments Off on What are Stem Cells? – Types, Applications and Sources | December 23rd, 2021

While stem cell therapies have been touted as miracle cures, data indicates that there are still hurdles keeping them out of the clinic.

Image credit: Getty Images/Hero Images

Stem cells have the unique ability to develop into a number of different and specialized cells. They can be thought of as the bodys raw material, ready for use when needed. With this comes their potential use in medicine as a means of repairing diseased or damaged tissue.

Consequently, stem cell therapy has generated intense interest, with a staggering 2600 clinical studies registered in the last 10 years alone. However, while these studies performed in both humans and animals have provided insight into potential benefits, the overall consensus is that they have yet to live up to their initial promise.

Currently, the only stem cell treatments that have FDA approval consist of blood-forming stem cells or hematopoietic progenitor cells derived from umbilical cord blood. These help restore blood-forming stem cells in cancer patients whose bone marrow cells have been destroyed by high doses of chemo-or radiation therapy.

Outside of this, clinical translation has seemingly been hampered. Its therefore important to ask: Are stem cells a source of hope or are they just hype?

The problem within this realm of scientific literature is conflicting study outcomes, says Hang Thu Ta, professor at Griffith University in Queensland, Australia and expert in biomedical engineering in the context of diagnosing and treating life-threatening diseases. Many studies demonstrate the desired, beneficial outcomes, but many others also demonstrate only modest or even negligible benefits.

For example, a review from 2016 exploring progress in cardiac stem cell regenerative therapy using adult stem cells found a lack of significant benefit. The analysis included 29 randomized clinical trials and seven systematic reviews and meta-analyses.

This could be explained by variations in trial methodology or discrepancies in reporting, but a major issue within the field is a lingering inability to track stem cells once they enter the body.

In a typical procedure, a large number of cells are infused through a single injection and repeated doses are given accordingly to maintain optimal therapeutic levels. Guided by biological cues or signals (like specific cytokines or growth factors), stem cells are expected to travel towards the diseased or injured location where they would stimulate regeneration of healthy tissue.

This happens naturally in the body, however, more often than not, researchers cannot definitively track their cells distribution and accumulation after they are transplanted artificially, said Shehzahdi Shebbrin Moonshi, a research fellow at the Queensland Micro- and Nanotechnology Centre at Griffith University and co-author of a recent study with Ta exploring the challenges that stem cell research is facing.

This puts a lot of guesswork into optimizing regimens and troubleshooting problems. Researchers are hard pressed to answer questions such as, where do the cells actually go? Do they migrate to the expected location? How long does this take? How many cells reach the target location?

The answers to all these questions cannot be known unless stem cells are monitored in real time after implantation. If stem cells arent where they need to be, then therapeutic effects aside, they cannot be properly exploited.

To solve this problem, clinicians and researchers need to be able to track stem cells in the body safely over prolonged periods of time.

Developments in this area have been growing in recent years. To this end, MRI is emerging as one of the safest and most suitable medical imaging techniques for this purpose. This is made possible using chemical tracers that make labelled stem cells visible in an MRI scan.

While there are many clinical trials being designed to monitor stem cells in the treatment of various diseases, MRI is [currently being] utilized in these studies as an imaging modality to monitor treatment efficacy and not to track implanted cells, said Ta. Therefore, it is crucial that we develop reliable and safe MRI tracers so we can get to the bottom of this.

There have been several preclinical studies involving the development of novel MRI cell tracers. These have included iron oxide nanoparticles and fluorinated nanoparticles that are attached to the cells.

Only one has really shown promise and has progressed to Phase I clinical trials, where iron-oxide labelled mesenchymal stromal cells were successfully tracked in patients with chronic heart disease, said Moonshi. The treatment was found to be safe, and cells were detectable at injection sites up to 14 days after transplantation.

MRI is even being combined with new technologies, such as optogenetics, which employs laser light to stimulate specific cells that have been rendered sensitive to particular frequencies of light.

Whilst MRI itself presents as a suitable imaging technique that allows visualization and monitoring of stem cells, a single modality is insufficient to obtain all vital data of implanted cells, said Moonshi. Therefore, combining different imaging modalities to track stem cells can overcome shortcomings involved with individual techniques.

This would provide scientists with a better understanding of effective dose, number of cells injected, and how effective they are at reaching their target location, added Ta. Going forward, this will allow researchers to explore best practices for achieving the greatest therapeutic outcome.

This article was contributed to by Shehzahdi Moonshi and Hang Ta

Reference: Shehzahdi Shebbrin Moonshi, Yuao Wu, Hang Thu Ta. Visualising Stem Cells In Vivo using Magnetic Resonance Imaging, WIRES Nanomed. Nanobiotechnol (2021). DOI: 10.1002/wnan.1760

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Are stem cells just hype? - Advanced Science News

Cardiac Stem Cells Comments Off on Are stem cells just hype? – Advanced Science News | December 23rd, 2021

Int J Cell Biol. 2016; 2016: 6940283.

Department of Biological Sciences, Indian Institute of Science Education and Research (IISER), Bhopal, Madhya Pradesh 462066, India

Department of Biological Sciences, Indian Institute of Science Education and Research (IISER), Bhopal, Madhya Pradesh 462066, India

Academic Editor: Paul J. Higgins

Received 2016 Mar 13; Accepted 2016 Jun 5.

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Regenerative medicine, the most recent and emerging branch of medical science, deals with functional restoration of tissues or organs for the patient suffering from severe injuries or chronic disease. The spectacular progress in the field of stem cell research has laid the foundation for cell based therapies of disease which cannot be cured by conventional medicines. The indefinite self-renewal and potential to differentiate into other types of cells represent stem cells as frontiers of regenerative medicine. The transdifferentiating potential of stem cells varies with source and according to that regenerative applications also change. Advancements in gene editing and tissue engineering technology have endorsed the ex vivo remodelling of stem cells grown into 3D organoids and tissue structures for personalized applications. This review outlines the most recent advancement in transplantation and tissue engineering technologies of ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs in regenerative medicine. Additionally, this review also discusses stem cells regenerative application in wildlife conservation.

Regenerative medicine, the most recent and emerging branch of medical science, deals with functional restoration of specific tissue and/or organ of the patients suffering with severe injuries or chronic disease conditions, in the state where bodies own regenerative responses do not suffice [1]. In the present scenario donated tissues and organs cannot meet the transplantation demands of aged and diseased populations that have driven the thrust for search for the alternatives. Stem cells are endorsed with indefinite cell division potential, can transdifferentiate into other types of cells, and have emerged as frontline regenerative medicine source in recent time, for reparation of tissues and organs anomalies occurring due to congenital defects, disease, and age associated effects [1]. Stem cells pave foundation for all tissue and organ system of the body and mediates diverse role in disease progression, development, and tissue repair processes in host. On the basis of transdifferentiation potential, stem cells are of four types, that is, (1) unipotent, (2) multipotent, (3) pluripotent, and (4) totipotent [2]. Zygote, the only totipotent stem cell in human body, can give rise to whole organism through the process of transdifferentiation, while cells from inner cells mass (ICM) of embryo are pluripotent in their nature and can differentiate into cells representing three germ layers but do not differentiate into cells of extraembryonic tissue [2]. Stemness and transdifferentiation potential of the embryonic, extraembryonic, fetal, or adult stem cells depend on functional status of pluripotency factors like OCT4, cMYC, KLF44, NANOG, SOX2, and so forth [35]. Ectopic expression or functional restoration of endogenous pluripotency factors epigenetically transforms terminally differentiated cells into ESCs-like cells [3], known as induced pluripotent stem cells (iPSCs) [3, 4]. On the basis of regenerative applications, stem cells can be categorized as embryonic stem cells (ESCs), tissue specific progenitor stem cells (TSPSCs), mesenchymal stem cells (MSCs), umbilical cord stem cells (UCSCs), bone marrow stem cells (BMSCs), and iPSCs (; ). The transplantation of stem cells can be autologous, allogenic, and syngeneic for induction of tissue regeneration and immunolysis of pathogen or malignant cells. For avoiding the consequences of host-versus-graft rejections, tissue typing of human leucocyte antigens (HLA) for tissue and organ transplant as well as use of immune suppressant is recommended [6]. Stem cells express major histocompatibility complex (MHC) receptor in low and secret chemokine that recruitment of endothelial and immune cells is enabling tissue tolerance at graft site [6]. The current stem cell regenerative medicine approaches are founded onto tissue engineering technologies that combine the principles of cell transplantation, material science, and microengineering for development of organoid; those can be used for physiological restoration of damaged tissue and organs. The tissue engineering technology generates nascent tissue on biodegradable 3D-scaffolds [7, 8]. The ideal scaffolds support cell adhesion and ingrowths, mimic mechanics of target tissue, support angiogenesis and neovascularisation for appropriate tissue perfusion, and, being nonimmunogenic to host, do not require systemic immune suppressant [9]. Stem cells number in tissue transplant impacts upon regenerative outcome [10]; in that case prior ex vivo expansion of transplantable stem cells is required [11]. For successful regenerative outcomes, transplanted stem cells must survive, proliferate, and differentiate in site specific manner and integrate into host circulatory system [12]. This review provides framework of most recent (; Figures ) advancement in transplantation and tissue engineering technologies of ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs in regenerative medicine. Additionally, this review also discusses stem cells as the tool of regenerative applications in wildlife conservation.

Promises of stem cells in regenerative medicine: the six classes of stem cells, that is, embryonic stem cells (ESCs), tissue specific progenitor stem cells (TSPSCs), mesenchymal stem cells (MSCs), umbilical cord stem cells (UCSCs), bone marrow stem cells (BMSCs), and induced pluripotent stem cells (iPSCs), have many promises in regenerative medicine and disease therapeutics.

ESCs in regenerative medicine: ESCs, sourced from ICM of gastrula, have tremendous promises in regenerative medicine. These cells can differentiate into more than 200 types of cells representing three germ layers. With defined culture conditions, ESCs can be transformed into hepatocytes, retinal ganglion cells, chondrocytes, pancreatic progenitor cells, cone cells, cardiomyocytes, pacemaker cells, eggs, and sperms which can be used in regeneration of tissue and treatment of disease in tissue specific manner.

TSPSCs in regenerative medicine: tissue specific stem and progenitor cells have potential to differentiate into other cells of the tissue. Characteristically inner ear stem cells can be transformed into auditory hair cells, skin progenitors into vascular smooth muscle cells, mesoangioblasts into tibialis anterior muscles, and dental pulp stem cells into serotonin cells. The 3D-culture of TSPSCs in complex biomaterial gives rise to tissue organoids, such as pancreatic organoid from pancreatic progenitor, intestinal tissue organoids from intestinal progenitor cells, and fallopian tube organoids from fallopian tube epithelial cells. Transplantation of TSPSCs regenerates targets tissue such as regeneration of tibialis muscles from mesoangioblasts, cardiac tissue from AdSCs, and corneal tissue from limbal stem cells. Cell growth and transformation factors secreted by TSPSCs can change cells fate to become other types of cell, such that SSCs coculture with skin, prostate, and intestine mesenchyme transforms these cells from MSCs into epithelial cells fate.

MSCs in regenerative medicine: mesenchymal stem cells are CD73+, CD90+, CD105+, CD34, CD45, CD11b, CD14, CD19, and CD79a cells, also known as stromal cells. These bodily MSCs represented here do not account for MSCs of bone marrow and umbilical cord. Upon transplantation and transdifferentiation these bodily MSCs regenerate into cartilage, bones, and muscles tissue. Heart scar formed after heart attack and liver cirrhosis can be treated from MSCs. ECM coating provides the niche environment for MSCs to regenerate into hair follicle, stimulating hair growth.

UCSCs in regenerative medicine: umbilical cord, the readily available source of stem cells, has emerged as futuristic source for personalized stem cell therapy. Transplantation of UCSCs to Krabbe's disease patients regenerates myelin tissue and recovers neuroblastoma patients through restoring tissue homeostasis. The UCSCs organoids are readily available tissue source for treatment of neurodegenerative disease. Peritoneal fibrosis caused by long term dialysis, tendon tissue degeneration, and defective hyaline cartilage can be regenerated by UCSCs. Intravenous injection of UCSCs enables treatment of diabetes, spinal myelitis, systemic lupus erythematosus, Hodgkin's lymphoma, and congenital neuropathies. Cord blood stem cells banking avails long lasting source of stem cells for personalized therapy and regenerative medicine.

BMSCs in regenerative medicine: bone marrow, the soft sponge bone tissue that consisted of stromal, hematopoietic, and mesenchymal and progenitor stem cells, is responsible for blood formation. Even halo-HLA matched BMSCs can cure from disease and regenerate tissue. BMSCs can regenerate craniofacial tissue, brain tissue, diaphragm tissue, and liver tissue and restore erectile function and transdifferentiation monocytes. These multipotent stem cells can cure host from cancer and infection of HIV and HCV.

iPSCs in regenerative medicine: using the edge of iPSCs technology, skin fibroblasts and other adult tissues derived, terminally differentiated cells can be transformed into ESCs-like cells. It is possible that adult cells can be transformed into cells of distinct lineages bypassing the phase of pluripotency. The tissue specific defined culture can transform skin cells to become trophoblast, heart valve cells, photoreceptor cells, immune cells, melanocytes, and so forth. ECM complexation with iPSCs enables generation of tissue organoids for lung, kidney, brain, and other organs of the body. Similar to ESCs, iPSCs also can be transformed into cells representing three germ layers such as pacemaker cells and serotonin cells.

Stem cells in wildlife conservation: tissue biopsies obtained from dead and live wild animals can be either cryopreserved or transdifferentiated to other types of cells, through culture in defined culture medium or in vivo maturation. Stem cells and adult tissue derived iPSCs have great potential of regenerative medicine and disease therapeutics. Gonadal tissue procured from dead wild animals can be matured, ex vivo and in vivo for generation of sperm and egg, which can be used for assistive reproductive technology oriented captive breeding of wild animals or even for resurrection of wildlife.

Application of stem cells in regenerative medicine: stem cells (ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs) have diverse applications in tissue regeneration and disease therapeutics.

For the first time in 1998, Thomson isolated human ESCs (hESCs) [13]. ESCs are pluripotent in their nature and can give rise to more than 200 types of cells and promises for the treatment of any kinds of disease [13]. The pluripotency fate of ESCs is governed by functional dynamics of transcription factors OCT4, SOX2, NANOG, and so forth, which are termed as pluripotency factors. The two alleles of the OCT4 are held apart in pluripotency state in ESCs; phase through homologues pairing during embryogenesis and transdifferentiation processes [14] has been considered as critical regulatory switch for lineage commitment of ESCs. The diverse lineage commitment potential represents ESCs as ideal model for regenerative therapeutics of disease and tissue anomalies. This section of review on ESCs discusses transplantation and transdifferentiation of ESCs into retinal ganglion, hepatocytes, cardiomyocytes, pancreatic progenitors, chondrocytes, cones, egg sperm, and pacemaker cells (; ). Infection, cancer treatment, and accidents can cause spinal cord injuries (SCIs). The transplantation of hESCs to paraplegic or quadriplegic SCI patients improves body control, balance, sensation, and limbal movements [15], where transplanted stem cells do homing to injury sites. By birth, humans have fixed numbers of cone cells; degeneration of retinal pigment epithelium (RPE) of macula in central retina causes age-related macular degeneration (ARMD). The genomic incorporation of COCO gene (expressed during embryogenesis) in the developing embryo leads lineage commitment of ESCs into cone cells, through suppression of TGF, BMP, and Wnt signalling pathways. Transplantation of these cone cells to eye recovers individual from ARMD phenomenon, where transplanted cone cells migrate and form sheet-like structure in host retina [16]. However, establishment of missing neuronal connection of retinal ganglion cells (RGCs), cones, and PRE is the most challenging aspect of ARMD therapeutics. Recently, Donald Z Jacks group at John Hopkins University School of Medicine has generated RGCs from CRISPER-Cas9-m-Cherry reporter ESCs [17]. During ESCs transdifferentiation process, CRIPER-Cas9 directs the knock-in of m-Cherry reporter into 3UTR of BRN3B gene, which is specifically expressed in RGCs and can be used for purification of generated RGCs from other cells [17]. Furthermore, incorporation of forskolin in transdifferentiation regime boosts generation of RGCs. Coaxing of these RGCs into biomaterial scaffolds directs axonal differentiation of RGCs. Further modification in RGCs generation regime and composition of biomaterial scaffolds might enable restoration of vision for ARMD and glaucoma patients [17]. Globally, especially in India, cardiovascular problems are a more common cause of human death, where biomedical therapeutics require immediate restoration of heart functions for the very survival of the patient. Regeneration of cardiac tissue can be achieved by transplantation of cardiomyocytes, ESCs-derived cardiovascular progenitors, and bone marrow derived mononuclear cells (BMDMNCs); however healing by cardiomyocytes and progenitor cells is superior to BMDMNCs but mature cardiomyocytes have higher tissue healing potential, suppress heart arrhythmias, couple electromagnetically into hearts functions, and provide mechanical and electrical repair without any associated tumorigenic effects [18, 19]. Like CM differentiation, ESCs derived liver stem cells can be transformed into Cytp450-hepatocytes, mediating chemical modification and catabolism of toxic xenobiotic drugs [20]. Even today, availability and variability of functional hepatocytes are a major a challenge for testing drug toxicity [20]. Stimulation of ESCs and ex vivo VitK12 and lithocholic acid (a by-product of intestinal flora regulating drug metabolism during infancy) activates pregnane X receptor (PXR), CYP3A4, and CYP2C9, which leads to differentiation of ESCs into hepatocytes; those are functionally similar to primary hepatocytes, for their ability to produce albumin and apolipoprotein B100 [20]. These hepatocytes are excellent source for the endpoint screening of drugs for accurate prediction of clinical outcomes [20]. Generation of hepatic cells from ESCs can be achieved in multiple ways, as serum-free differentiation [21], chemical approaches [20, 22], and genetic transformation [23, 24]. These ESCs-derived hepatocytes are long lasting source for treatment of liver injuries and high throughput screening of drugs [20, 23, 24]. Transplantation of the inert biomaterial encapsulated hESCs-derived pancreatic progenitors (CD24+, CD49+, and CD133+) differentiates into -cells, minimizing high fat diet induced glycemic and obesity effects in mice [25] (). Addition of antidiabetic drugs into transdifferentiation regime can boost ESCs conservation into -cells [25], which theoretically can cure T2DM permanently [25]. ESCs can be differentiated directly into insulin secreting -cells (marked with GLUT2, INS1, GCK, and PDX1) which can be achieved through PDX1 mediated epigenetic reprogramming [26]. Globally, osteoarthritis affects millions of people and occurs when cartilage at joints wears away, causing stiffness of the joints. The available therapeutics for arthritis relieve symptoms but do not initiate reverse generation of cartilage. For young individuals and athletes replacement of joints is not feasible like old populations; in that case transplantation of stem cells represents an alternative for healing cartilage injuries [27]. Chondrocytes, the cartilage forming cells derived from hESC, embedded in fibrin gel effectively heal defective cartilage within 12 weeks, when transplanted to focal cartilage defects of knee joints in mice without any negative effect [27]. Transplanted chondrocytes form cell aggregates, positive for SOX9 and collagen II, and defined chondrocytes are active for more than 12wks at transplantation site, advocating clinical suitability of chondrocytes for treatment of cartilage lesions [27]. The integrity of ESCs to integrate and differentiate into electrophysiologically active cells provides a means for natural regulation of heart rhythm as biological pacemaker. Coaxing of ESCs into inert biomaterial as well as propagation in defined culture conditions leads to transdifferentiation of ESCs to become sinoatrial node (SAN) pacemaker cells (PCs) [28]. Genomic incorporation TBox3 into ESCs ex vivo leads to generation of PCs-like cells; those express activated leukocyte cells adhesion molecules (ALCAM) and exhibit similarity to PCs for gene expression and immune functions [28]. Transplantation of PCs can restore pacemaker functions of the ailing heart [28]. In summary, ESCs can be transdifferentiated into any kinds of cells representing three germ layers of the body, being most promising source of regenerative medicine for tissue regeneration and disease therapy (). Ethical concerns limit the applications of ESCs, where set guidelines need to be followed; in that case TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs can be explored as alternatives.

TSPSCs maintain tissue homeostasis through continuous cell division, but, unlike ESCs, TSPSCs retain stem cells plasticity and differentiation in tissue specific manner, giving rise to few types of cells (). The number of TSPSCs population to total cells population is too low; in that case their harvesting as well as in vitro manipulation is really a tricky task [29], to explore them for therapeutic scale. Human body has foundation from various types of TSPSCs; discussing the therapeutic application for all types is not feasible. This section of review discusses therapeutic application of pancreatic progenitor cells (PPCs), dental pulp stem cells (DPSCs), inner ear stem cells (IESCs), intestinal progenitor cells (IPCs), limbal progenitor stem cells (LPSCs), epithelial progenitor stem cells (EPSCs), mesoangioblasts (MABs), spermatogonial stem cells (SSCs), the skin derived precursors (SKPs), and adipose derived stem cells (AdSCs) (; ). During embryogenesis PPCs give rise to insulin-producing -cells. The differentiation of PPCs to become -cells is negatively regulated by insulin [30]. PPCs require active FGF and Notch signalling; growing more rapidly in community than in single cell populations advocates the functional importance of niche effect in self-renewal and transdifferentiation processes. In 3D-scaffold culture system, mice embryo derived PPCs grow into hollow organoid spheres; those finally differentiate into insulin-producing -cell clusters [29]. The DSPSCs, responsible for maintenance of teeth health status, can be sourced from apical papilla, deciduous teeth, dental follicle, and periodontal ligaments, have emerged as regenerative medicine candidate, and might be explored for treatment of various kinds of disease including restoration neurogenic functions in teeth [31, 32]. Expansion of DSPSCs in chemically defined neuronal culture medium transforms them into a mixed population of cholinergic, GABAergic, and glutaminergic neurons; those are known to respond towards acetylcholine, GABA, and glutamine stimulations in vivo. These transformed neuronal cells express nestin, glial fibrillary acidic protein (GFAP), III-tubulin, and voltage gated L-type Ca2+ channels [32]. However, absence of Na+ and K+ channels does not support spontaneous action potential generation, necessary for response generation against environmental stimulus. All together, these primordial neuronal stem cells have possible therapeutic potential for treatment of neurodental problems [32]. Sometimes, brain tumor chemotherapy can cause neurodegeneration mediated cognitive impairment, a condition known as chemobrain [33]. The intrahippocampal transplantation of human derived neuronal stem cells to cyclophosphamide behavioural decremented mice restores cognitive functions in a month time. Here the transplanted stem cells differentiate into neuronal and astroglial lineage, reduce neuroinflammation, and restore microglial functions [33]. Furthermore, transplantation of stem cells, followed by chemotherapy, directs pyramidal and granule-cell neurons of the gyrus and CA1 subfields of hippocampus which leads to reduction in spine and dendritic cell density in the brain. These findings suggest that transplantation of stem cells to cranium restores cognitive functions of the chemobrain [33]. The hair cells of the auditory system produced during development are not postmitotic; loss of hair cells cannot be replaced by inner ear stem cells, due to active state of the Notch signalling [34]. Stimulation of inner ear progenitors with -secretase inhibitor ({"type":"entrez-nucleotide","attrs":{"text":"LY411575","term_id":"1257853995","term_text":"LY411575"}}LY411575) abrogates Notch signalling through activation of transcription factor atonal homologue 1 (Atoh1) and directs transdifferentiation of progenitors into cochlear hair cells [34]. Transplantation of in vitro generated hair cells restores acoustic functions in mice, which can be the potential regenerative medicine candidates for the treatment of deafness [34]. Generation of the hair cells also can be achieved through overexpression of -catenin and Atoh1 in Lrg5+ cells in vivo [35]. Similar to ear progenitors, intestine of the digestive tract also has its own tissue specific progenitor stem cells, mediating regeneration of the intestinal tissue [34, 36]. Dysregulation of the common stem cells signalling pathways, Notch/BMP/TGF-/Wnt, in the intestinal tissue leads to disease. Information on these signalling pathways [37] is critically important in designing therapeutics. Coaxing of the intestinal tissue specific progenitors with immune cells (macrophages), connective tissue cells (myofibroblasts), and probiotic bacteria into 3D-scaffolds of inert biomaterial, crafting biological environment, is suitable for differentiation of progenitors to occupy the crypt-villi structures into these scaffolds [36]. Omental implementation of these crypt-villi structures to dogs enhances intestinal mucosa through regeneration of goblet cells containing intestinal tissue [36]. These intestinal scaffolds are close approach for generation of implantable intestinal tissue, divested by infection, trauma, cancer, necrotizing enterocolitis (NEC), and so forth [36]. In vitro culture conditions cause differentiation of intestinal stem cells to become other types of cells, whereas incorporation of valproic acid and CHIR-99021 in culture conditions avoids differentiation of intestinal stem cells, enabling generation of indefinite pool of stem cells to be used for regenerative applications [38]. The limbal stem cells of the basal limbal epithelium, marked with ABCB5, are essential for regeneration and maintenance of corneal tissue [39]. Functional status of ABCB5 is critical for survival and functional integrity of limbal stem cells, protecting them from apoptotic cell death [39]. Limbal stem cells deficiency leads to replacement of corneal epithelium with visually dead conjunctival tissue, which can be contributed by burns, inflammation, and genetic factors [40]. Transplanted human cornea stem cells to mice regrown into fully functional human cornea, possibly supported by blood eye barrier phenomena, can be used for treatment of eye diseases, where regeneration of corneal tissue is critically required for vision restoration [39]. Muscle degenerative disease like duchenne muscular dystrophy (DMD) can cause extensive thrashing of muscle tissue, where tissue engineering technology can be deployed for functional restoration of tissue through regeneration [41]. Encapsulation of mouse or human derived MABs (engineered to express placental derived growth factor (PDGF)) into polyethylene glycol (PEG) fibrinogen hydrogel and their transplantation beneath the skin at ablated tibialis anterior form artificial muscles, which are functionally similar to those of normal tibialis anterior muscles [41]. The PDGF attracts various cell types of vasculogenic and neurogenic potential to the site of transplantation, supporting transdifferentiation of mesoangioblasts to become muscle fibrils [41]. The therapeutic application of MABs in skeletal muscle regeneration and other therapeutic outcomes has been reviewed by others [42]. One of the most important tissue specific stem cells, the male germline stem cells or spermatogonial stem cells (SSCs), produces spermatogenic lineage through mesenchymal and epithets cells [43] which itself creates niche effect on other cells. In vivo transplantation of SSCs with prostate, skin, and uterine mesenchyme leads to differentiation of these cells to become epithelia of the tissue of origin [43]. These newly formed tissues exhibit all physical and physiological characteristics of prostate and skin and the physical characteristics of prostate, skin, and uterus, express tissue specific markers, and suggest that factors secreted from SSCs lead to lineage conservation which defines the importance of niche effect in regenerative medicine [43]. According to an estimate, more than 100 million people are suffering from the condition of diabetic retinopathy, a progressive dropout of vascularisation in retina that leads to loss of vision [44]. The intravitreal injection of adipose derived stem cells (AdSCs) to the eye restores microvascular capillary bed in mice. The AdSCs from healthy donor produce higher amounts of vasoprotective factors compared to glycemic mice, enabling superior vascularisation [44]. However use of AdSCs for disease therapeutics needs further standardization for cell counts in dose of transplant and monitoring of therapeutic outcomes at population scale [44]. Apart from AdSCs, other kinds of stem cells also have therapeutic potential in regenerative medicine for treatment of eye defects, which has been reviewed by others [45]. Fallopian tubes, connecting ovaries to uterus, are the sites where fertilization of the egg takes place. Infection in fallopian tubes can lead to inflammation, tissue scarring, and closure of the fallopian tube which often leads to infertility and ectopic pregnancies. Fallopian is also the site where onset of ovarian cancer takes place. The studies on origin and etiology of ovarian cancer are restricted due to lack of technical advancement for culture of epithelial cells. The in vitro 3D organoid culture of clinically obtained fallopian tube epithelial cells retains their tissue specificity, keeps cells alive, which differentiate into typical ciliated and secretory cells of fallopian tube, and advocates that ectopic examination of fallopian tube in organoid culture settings might be the ideal approach for screening of cancer [46]. The sustained growth and differentiation of fallopian TSPSCs into fallopian tube organoid depend both on the active state of the Wnt and on paracrine Notch signalling [46]. Similar to fallopian tube stem cells, subcutaneous visceral tissue specific cardiac adipose (CA) derived stem cells (AdSCs) have the potential of differentiation into cardiovascular tissue [47]. Systemic infusion of CA-AdSCs into ischemic myocardium of mice regenerates heart tissue and improves cardiac function through differentiation to endothelial cells, vascular smooth cells, and cardiomyocytes and vascular smooth cells. The differentiation and heart regeneration potential of CA-AdSCs are higher than AdSCs [48], representing CA-AdSCs as potent regenerative medicine candidates for myocardial ischemic therapy [47]. The skin derived precursors (SKPs), the progenitors of dermal papilla/hair/hair sheath, give rise to multiple tissues of mesodermal and/or ectodermal origin such as neurons, Schwann cells, adipocytes, chondrocytes, and vascular smooth muscle cells (VSMCs). VSMCs mediate wound healing and angiogenesis process can be derived from human foreskin progenitor SKPs, suggesting that SKPs derived VSMCs are potential regenerative medicine candidates for wound healing and vasculature injuries treatments [49]. In summary, TSPSCs are potentiated with tissue regeneration, where advancement in organoid culture (; ) technologies defines the importance of niche effect in tissue regeneration and therapeutic outcomes of ex vivo expanded stem cells.

MSCs, the multilineage stem cells, differentiate only to tissue of mesodermal origin, which includes tendons, bone, cartilage, ligaments, muscles, and neurons [50]. MSCs are the cells which express combination of markers: CD73+, CD90+, CD105+, CD11b, CD14, CD19, CD34, CD45, CD79a, and HLA-DR, reviewed elsewhere [50]. The application of MSCs in regenerative medicine can be generalized from ongoing clinical trials, phasing through different state of completions, reviewed elsewhere [90]. This section of review outlines the most recent representative applications of MSCs (; ). The anatomical and physiological characteristics of both donor and receiver have equal impact on therapeutic outcomes. The bone marrow derived MSCs (BMDMSCs) from baboon are morphologically and phenotypically similar to those of bladder stem cells and can be used in regeneration of bladder tissue. The BMDMSCs (CD105+, CD73+, CD34, and CD45), expressing GFP reporter, coaxed with small intestinal submucosa (SIS) scaffolds, augment healing of degenerated bladder tissue within 10wks of the transplantation [51]. The combinatorial CD characterized MACs are functionally active at transplantation site, which suggests that CD characterization of donor MSCs yields superior regenerative outcomes [51]. MSCs also have potential to regenerate liver tissue and treat liver cirrhosis, reviewed elsewhere [91]. The regenerative medicinal application of MSCs utilizes cells in two formats as direct transplantation or first transdifferentiation and then transplantation; ex vivo transdifferentiation of MSCs deploys retroviral delivery system that can cause oncogenic effect on cells. Nonviral, NanoScript technology, comprising utility of transcription factors (TFs) functionalized gold nanoparticles, can target specific regulatory site in the genome effectively and direct differentiation of MSCs into another cell fate, depending on regime of TFs. For example, myogenic regulatory factor containing NanoScript-MRF differentiates the adipose tissue derived MSCs into muscle cells [92]. The multipotency characteristics represent MSCs as promising candidate for obtaining stable tissue constructs through coaxed 3D organoid culture; however heterogeneous distribution of MSCs slows down cell proliferation, rendering therapeutic applications of MSCs. Adopting two-step culture system for MSCs can yield homogeneous distribution of MSCs in biomaterial scaffolds. For example, fetal-MSCs coaxed in biomaterial when cultured first in rotating bioreactor followed with static culture lead to homogeneous distribution of MSCs in ECM components [7]. Occurrence of dental carries, periodontal disease, and tooth injury can impact individual's health, where bioengineering of teeth can be the alternative option. Coaxing of epithelial-MSCs with dental stem cells into synthetic polymer gives rise to mature teeth unit, which consisted of mature teeth and oral tissue, offering multiple regenerative therapeutics, reviewed elsewhere [52]. Like the tooth decay, both human and animals are prone to orthopedic injuries, affecting bones, joint, tendon, muscles, cartilage, and so forth. Although natural healing potential of bone is sufficient to heal the common injuries, severe trauma and tumor-recession can abrogate germinal potential of bone-forming stem cells. In vitro chondrogenic, osteogenic, and adipogenic potential of MSCs advocates therapeutic applications of MSCs in orthopedic injuries [53]. Seeding of MSCs, coaxed into biomaterial scaffolds, at defective bone tissue, regenerates defective bone tissues, within fourwks of transplantation; by the end of 32wks newly formed tissues integrate into old bone [54]. Osteoblasts, the bone-forming cells, have lesser actin cytoskeleton compared to adipocytes and MSCs. Treatment of MSCs with cytochalasin-D causes rapid transportation of G-actin, leading to osteogenic transformation of MSCs. Furthermore, injection of cytochalasin-D to mice tibia also promotes bone formation within a wk time frame [55]. The bone formation processes in mice, dog, and human are fundamentally similar, so outcomes of research on mice and dogs can be directional for regenerative application to human. Injection of MSCs to femur head of Legg-Calve-Perthes suffering dog heals the bone very fast and reduces the injury associated pain [55]. Degeneration of skeletal muscle and muscle cramps are very common to sledge dogs, animals, and individuals involved in adventurous athletics activities. Direct injection of adipose tissue derived MSCs to tear-site of semitendinosus muscle in dogs heals injuries much faster than traditional therapies [56]. Damage effect treatment for heart muscle regeneration is much more complex than regeneration of skeletal muscles, which needs high grade fine-tuned coordination of neurons with muscles. Coaxing of MSCs into alginate gel increases cell retention time that leads to releasing of tissue repairing factors in controlled manner. Transplantation of alginate encapsulated cells to mice heart reduces scar size and increases vascularisation, which leads to restoration of heart functions. Furthermore, transplanted MSCs face host inhospitable inflammatory immune responses and other mechanical forces at transplantation site, where encapsulation of cells keeps them away from all sorts of mechanical forces and enables sensing of host tissue microenvironment, and respond accordingly [57]. Ageing, disease, and medicine consumption can cause hair loss, known as alopecia. Although alopecia has no life threatening effects, emotional catchments can lead to psychological disturbance. The available treatments for alopecia include hair transplantation and use of drugs, where drugs are expensive to afford and generation of new hair follicle is challenging. Dermal papillary cells (DPCs), the specialized MSCs localized in hair follicle, are responsible for morphogenesis of hair follicle and hair cycling. The layer-by-layer coating of DPCs, called GAG coating, consists of coating of geletin as outer layer, middle layer of fibroblast growth factor 2 (FGF2) loaded alginate, and innermost layer of geletin. GAG coating creates tissue microenvironment for DPCs that can sustain immunological and mechanical obstacles, supporting generation of hair follicle. Transplantation of GAG-coated DPCs leads to abundant hair growth and maturation of hair follicle, where GAG coating serves as ECM, enhancing intrinsic therapeutic potential of DPCs [58]. During infection, the inflammatory cytokines secreted from host immune cells attract MSCs to the site of inflammation, which modulates inflammatory responses, representing MSCs as key candidate of regenerative medicine for infectious disease therapeutics. Coculture of macrophages (M) and adipose derived MSCs from Leishmania major (LM) susceptible and resistant mice demonstrates that AD-MSCs educate M against LM infection, differentially inducing M1 and M2 phenotype that represents AD-MSC as therapeutic agent for leishmanial therapy [93]. In summary, the multilineage differentiation potential of MSCs, as well as adoption of next-generation organoid culture system, avails MSCs as ideal regenerative medicine candidate.

Umbilical cord, generally thrown at the time of child birth, is the best known source for stem cells, procured in noninvasive manner, having lesser ethical constraints than ESCs. Umbilical cord is rich source of hematopoietic stem cells (HSCs) and MSCs, which possess enormous regeneration potential [94] (; ). The HSCs of cord blood are responsible for constant renewal of all types of blood cells and protective immune cells. The proliferation of HSCs is regulated by Musashi-2 protein mediated attenuation of Aryl hydrocarbon receptor (AHR) signalling in stem cells [95]. UCSCs can be cryopreserved at stem cells banks (; ), in operation by both private and public sector organization. Public stem cells banks operate on donation formats and perform rigorous screening for HLA typing and donated UCSCs remain available to anyone in need, whereas private stem cell banks operation is more personalized, availing cells according to donor consent. Stem cell banking is not so common, even in developed countries. Survey studies find that educated women are more eager to donate UCSCs, but willingness for donation decreases with subsequent deliveries, due to associated cost and safety concerns for preservation [96]. FDA has approved five HSCs for treatment of blood and other immunological complications [97]. The amniotic fluid, drawn during pregnancy for standard diagnostic purposes, is generally discarded without considering its vasculogenic potential. UCSCs are the best alternatives for those patients who lack donors with fully matched HLA typing for peripheral blood and PBMCs and bone marrow [98]. One major issue with UCSCs is number of cells in transplant, fewer cells in transplant require more time for engraftment to mature, and there are also risks of infection and mortality; in that case ex vivo propagation of UCSCs can meet the demand of desired outcomes. There are diverse protocols, available for ex vivo expansion of UCSCs, reviewed elsewhere [99]. Amniotic fluid stem cells (AFSCs), coaxed to fibrin (required for blood clotting, ECM interactions, wound healing, and angiogenesis) hydrogel and PEG supplemented with vascular endothelial growth factor (VEGF), give rise to vascularised tissue, when grafted to mice, suggesting that organoid cultures of UCSCs have promise for generation of biocompatible tissue patches, for treating infants born with congenital heart defects [59]. Retroviral integration of OCT4, KLF4, cMYC, and SOX2 transforms AFSCs into pluripotency stem cells known as AFiPSCs which can be directed to differentiate into extraembryonic trophoblast by BMP2 and BMP4 stimulation, which can be used for regeneration of placental tissues [60]. Wharton's jelly (WJ), the gelatinous substance inside umbilical cord, is rich in mucopolysaccharides, fibroblast, macrophages, and stem cells. The stem cells from UCB and WJ can be transdifferentiated into -cells. Homogeneous nature of WJ-SCs enables better differentiation into -cells; transplantation of these cells to streptozotocin induced diabetic mice efficiently brings glucose level to normal [7]. Easy access and expansion potential and plasticity to differentiate into multiple cell lineages represent WJ as an ideal candidate for regenerative medicine but cells viability changes with passages with maximum viable population at 5th-6th passages. So it is suggested to perform controlled expansion of WJ-MSCS for desired regenerative outcomes [9]. Study suggests that CD34+ expression leads to the best regenerative outcomes, with less chance of host-versus-graft rejection. In vitro expansion of UCSCs, in presence of StemRegenin-1 (SR-1), conditionally expands CD34+ cells [61]. In type I diabetic mellitus (T1DM), T-cell mediated autoimmune destruction of pancreatic -cells occurs, which has been considered as tough to treat. Transplantation of WJ-SCs to recent onset-T1DM patients restores pancreatic function, suggesting that WJ-MSCs are effective in regeneration of pancreatic tissue anomalies [62]. WJ-MSCs also have therapeutic importance for treatment of T2DM. A non-placebo controlled phase I/II clinical trial demonstrates that intravenous and intrapancreatic endovascular injection of WJ-MSCs to T2DM patients controls fasting glucose and glycated haemoglobin through improvement of -cells functions, evidenced by enhanced c-peptides and reduced inflammatory cytokines (IL-1 and IL-6) and T-cells counts [63]. Like diabetes, systematic lupus erythematosus (SLE) also can be treated with WJ-MSCs transplantation. During progression of SLE host immune system targets its own tissue leading to degeneration of renal, cardiovascular, neuronal, and musculoskeletal tissues. A non-placebo controlled follow-up study on 40 SLE patients demonstrates that intravenous infusion of WJ-MSC improves renal functions and decreases systematic lupus erythematosus disease activity index (SLEDAI) and British Isles Lupus Assessment Group (BILAG), and repeated infusion of WJ-MSCs protects the patient from relapse of the disease [64]. Sometimes, host inflammatory immune responses can be detrimental for HSCs transplantation and blood transfusion procedures. Infusion of WJ-MSC to patients, who had allogenic HSCs transplantation, reduces haemorrhage inflammation (HI) of bladder, suggesting that WJ-MSCs are potential stem cells adjuvant in HSCs transplantation and blood transfusion based therapies [100]. Apart from WJ, umbilical cord perivascular space and cord vein are also rich source for obtaining MSCs. The perivascular MSCs of umbilical cord are more primitive than WJ-MSCs and other MSCs from cord suggest that perivascular MSCs might be used as alternatives for WJ-MSCs for regenerative therapeutics outcome [101]. Based on origin, MSCs exhibit differential in vitro and in vivo properties and advocate functional characterization of MSCs, prior to regenerative applications. Emerging evidence suggests that UCSCs can heal brain injuries, caused by neurodegenerative diseases like Alzheimer's, Krabbe's disease, and so forth. Krabbe's disease, the infantile lysosomal storage disease, occurs due to deficiency of myelin synthesizing enzyme (MSE), affecting brain development and cognitive functions. Progression of neurodegeneration finally leads to death of babies aged two. Investigation shows that healing of peripheral nervous system (PNS) and central nervous system (CNS) tissues with Krabbe's disease can be achieved by allogenic UCSCs. UCSCs transplantation to asymptomatic infants with subsequent monitoring for 46 years reveals that UCSCs recover babies from MSE deficiency, improving myelination and cognitive functions, compared to those of symptomatic babies. The survival rate of transplanted UCSCs in asymptomatic and symptomatic infants was 100% and 43%, respectively, suggesting that early diagnosis and timely treatment are critical for UCSCs acceptance for desired therapeutic outcomes. UCSCs are more primitive than BMSCs, so perfect HLA typing is not critically required, representing UCSCs as an excellent source for treatment of all the diseases involving lysosomal defects, like Krabbe's disease, hurler syndrome, adrenoleukodystrophy (ALD), metachromatic leukodystrophy (MLD), Tay-Sachs disease (TSD), and Sandhoff disease [65]. Brain injuries often lead to cavities formation, which can be treated from neuronal parenchyma, generated ex vivo from UCSCs. Coaxing of UCSCs into human originated biodegradable matrix scaffold and in vitro expansion of cells in defined culture conditions lead to formation of neuronal organoids, within threewks' time frame. These organoids structurally resemble brain tissue and consisted of neuroblasts (GFAP+, Nestin+, and Ki67+) and immature stem cells (OCT4+ and SOX2+). The neuroblasts of these organoids further can be differentiated into mature neurons (MAP2+ and TUJ1+) [66]. Administration of high dose of drugs in divesting neuroblastoma therapeutics requires immediate restoration of hematopoiesis. Although BMSCs had been promising in restoration of hematopoiesis UCSCs are sparely used in clinical settings. A case study demonstrates that neuroblastoma patients who received autologous UCSCs survive without any associated side effects [12]. During radiation therapy of neoplasm, spinal cord myelitis can occur, although occurrence of myelitis is a rare event and usually such neurodegenerative complication of spinal cord occurs 624 years after exposure to radiations. Transplantation of allogenic UC-MSCs in laryngeal patients undergoing radiation therapy restores myelination [102]. For treatment of neurodegenerative disease like Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), traumatic brain injuries (TBI), Parkinson's, SCI, stroke, and so forth, distribution of transplanted UCSCs is critical for therapeutic outcomes. In mice and rat, injection of UCSCs and subsequent MRI scanning show that transplanted UCSCs migrate to CNS and multiple peripheral organs [67]. For immunomodulation of tumor cells disease recovery, transplantation of allogenic DCs is required. The CD11c+DCs, derived from UCB, are morphologically and phenotypically similar to those of peripheral blood derived CTLs-DCs, suggesting that UCB-DCs can be used for personalized medicine of cancer patient, in need for DCs transplantation [103]. Coculture of UCSCs with radiation exposed human lung fibroblast stops their transdifferentiation, which suggests that factors secreted from UCSCs may restore niche identity of fibroblast, if they are transplanted to lung after radiation therapy [104]. Tearing of shoulder cuff tendon can cause severe pain and functional disability, whereas ultrasound guided transplantation of UCB-MSCs in rabbit regenerates subscapularis tendon in fourwks' time frame, suggesting that UCB-MSCs are effective enough to treat tendons injuries when injected to focal points of tear-site [68]. Furthermore, transplantation of UCB-MSCs to chondral cartilage injuries site in pig knee along with HA hydrogel composite regenerates hyaline cartilage [69], suggesting that UCB-MSCs are effective regenerative medicine candidate for treating cartilage and ligament injuries. Physiologically circulatory systems of brain, placenta, and lungs are similar. Infusion of UCB-MSCs to preeclampsia (PE) induced hypertension mice reduces the endotoxic effect, suggesting that UC-MSCs are potential source for treatment of endotoxin induced hypertension during pregnancy, drug abuse, and other kinds of inflammatory shocks [105]. Transplantation of UCSCs to severe congenital neutropenia (SCN) patients restores neutrophils count from donor cells without any side effect, representing UCSCs as potential alternative for SCN therapy, when HLA matched bone marrow donors are not accessible [106]. In clinical settings, the success of myocardial infarction (MI) treatment depends on ageing, systemic inflammation in host, and processing of cells for infusion. Infusion of human hyaluronan hydrogel coaxed UCSCs in pigs induces angiogenesis, decreases scar area, improves cardiac function at preclinical level, and suggests that the same strategy might be effective for human [107]. In stem cells therapeutics, UCSCs transplantation can be either autologous or allogenic. Sometimes, the autologous UCSCs transplants cannot combat over tumor relapse, observed in Hodgkin's lymphoma (HL), which might require second dose transplantation of allogenic stem cells, but efficacy and tolerance of stem cells transplant need to be addressed, where tumor replace occurs. A case study demonstrates that second dose allogenic transplants of UCSCs effective for HL patients, who had heavy dose in prior transplant, increase the long term survival chances by 30% [10]. Patients undergoing long term peritoneal renal dialysis are prone to peritoneal fibrosis and can change peritoneal structure and failure of ultrafiltration processes. The intraperitoneal (IP) injection of WJ-MSCs prevents methylglyoxal induced programmed cell death and peritoneal wall thickening and fibrosis, suggesting that WJ-MSCs are effective in therapeutics of encapsulating peritoneal fibrosis [70]. In summary, UCB-HSCs, WJ-MSCs, perivascular MSCs, and UCB-MSCs have tissue regeneration potential.

Bone marrow found in soft spongy bones is responsible for formation of all peripheral blood and comprises hematopoietic stem cells (producing blood cells) and stromal cells (producing fat, cartilage, and bones) [108] (; ). Visually bone marrow has two types, red marrow (myeloid tissue; producing RBC, platelets, and most of WBC) and yellow marrow (producing fat cells and some WBC) [108]. Imbalance in marrow composition can culminate to the diseased condition. Since 1980, bone marrow transplantation is widely accepted for cancer therapeutics [109]. In order to avoid graft rejection, HLA typing of donors is a must, but completely matched donors are limited to family members, which hampers allogenic transplantation applications. Since matching of all HLA antigens is not critically required, in that case defining the critical antigens for haploidentical allogenic donor for patients, who cannot find fully matched donor, might relieve from donor constraints. Two-step administration of lymphoid and myeloid BMSCs from haploidentical donor to the patients of aplastic anaemia and haematological malignancies reconstructs host immune system and the outcomes are almost similar to fully matched transplants, which recommends that profiling of critically important HLA is sufficient for successful outcomes of BMSCs transplantation. Haploidentical HLA matching protocol is the major process for minorities and others who do not have access to matched donor [71]. Furthermore, antigen profiling is not the sole concern for BMSCs based therapeutics. For example, restriction of HIV1 (human immune deficiency virus) infection is not feasible through BMSCs transplantation because HIV1 infection is mediated through CD4+ receptors, chemokine CXC motif receptor 4 (CXCR4), and chemokine receptor 5 (CCR5) for infecting and propagating into T helper (Th), monocytes, macrophages, and dendritic cells (DCs). Genetic variation in CCR2 and CCR5 receptors is also a contributory factor; mediating protection against infection has been reviewed elsewhere [110]. Engineering of hematopoietic stem and progenitor cells (HSPCs) derived CD4+ cells to express HIV1 antagonistic RNA, specifically designed for targeting HIV1 genome, can restrict HIV1 infection, through immune elimination of latently infected CD4+ cells. A single dose infusion of genetically modified (GM), HIV1 resistant HSPCs can be the alternative of HIV1 retroviral therapy. In the present scenario stem cells source, patient selection, transplantation-conditioning regimen, and postinfusion follow-up studies are the major factors, which can limit application of HIV1 resistant GM-HSPCs (CD4+) cells application in AIDS therapy [72, 73]. Platelets, essential for blood clotting, are formed from megakaryocytes inside the bone marrow [74]. Due to infection, trauma, and cancer, there are chances of bone marrow failure. To an extent, spongy bone marrow microenvironment responsible for lineage commitment can be reconstructed ex vivo [75]. The ex vivo constructed 3D-scaffolds consisted of microtubule and silk sponge, flooded with chemically defined organ culture medium, which mimics bone marrow environment. The coculture of megakaryocytes and embryonic stem cells (ESCs) in this microenvironment leads to generation of functional platelets from megakaryocytes [75]. The ex vivo 3D-scaffolds of bone microenvironment can stride the path for generation of platelets in therapeutic quantities for regenerative medication of burns [75] and blood clotting associated defects. Accidents, traumatic injuries, and brain stroke can deplete neuronal stem cells (NSCs), responsible for generation of neurons, astrocytes, and oligodendrocytes. Brain does not repopulate NSCs and heal traumatic injuries itself and transplantation of BMSCs also can heal neurodegeneration alone. Lipoic acid (LA), a known pharmacological antioxidant compound used in treatment of diabetic and multiple sclerosis neuropathy when combined with BMSCs, induces neovascularisation at focal cerebral injuries, within 8wks of transplantation. Vascularisation further attracts microglia and induces their colonization into scaffold, which leads to differentiation of BMSCs to become brain tissue, within 16wks of transplantation. In this approach, healing of tissue directly depends on number of BMSCs in transplantation dose [76]. Dental caries and periodontal disease are common craniofacial disease, often requiring jaw bone reconstruction after removal of the teeth. Traditional therapy focuses on functional and structural restoration of oral tissue, bone, and teeth rather than biological restoration, but BMSCs based therapies promise for regeneration of craniofacial bone defects, enabling replacement of missing teeth in restored bones with dental implants. Bone marrow derived CD14+ and CD90+ stem and progenitor cells, termed as tissue repair cells (TRC), accelerate alveolar bone regeneration and reconstruction of jaw bone when transplanted in damaged craniofacial tissue, earlier to oral implants. Hence, TRC therapy reduces the need of secondary bone grafts, best suited for severe defects in oral bone, skin, and gum, resulting from trauma, disease, or birth defects [77]. Overall, HSCs have great value in regenerative medicine, where stem cells transplantation strategies explore importance of niche in tissue regeneration. Prior to transplantation of BMSCs, clearance of original niche from target tissue is necessary for generation of organoid and organs without host-versus-graft rejection events. Some genetic defects can lead to disorganization of niche, leading to developmental errors. Complementation with human blastocyst derived primary cells can restore niche function of pancreas in pigs and rats, which defines the concept for generation of clinical grade human pancreas in mice and pigs [111]. Similar to other organs, diaphragm also has its own niche. Congenital defects in diaphragm can affect diaphragm functions. In the present scenario functional restoration of congenital diaphragm defects by surgical repair has risk of reoccurrence of defects or incomplete restoration [8]. Decellularization of donor derived diaphragm offers a way for reconstruction of new and functionally compatible diaphragm through niche modulation. Tissue engineering technology based decellularization of diaphragm and simultaneous perfusion of bone marrow mesenchymal stem cells (BM-MSCs) facilitates regeneration of functional scaffolds of diaphragm tissues [8]. In vivo replacement of hemidiaphragm in rats with reseeded scaffolds possesses similar myography and spirometry as it has in vivo in donor rats. These scaffolds retaining natural architecture are devoid of immune cells, retaining intact extracellular matrix that supports adhesion, proliferation, and differentiation of seeded cells [8]. These findings suggest that cadaver obtained diaphragm, seeded with BM-MSCs, can be used for curing patients in need for restoration of diaphragm functions (; ). However, BMSCs are heterogeneous population, which might result in differential outcomes in clinical settings; however clonal expansion of BMSCs yields homogenous cells population for therapeutic application [8]. One study also finds that intracavernous delivery of single clone BMSCs can restore erectile function in diabetic mice [112] and the same strategy might be explored for adult human individuals. The infection of hepatitis C virus (HCV) can cause liver cirrhosis and degeneration of hepatic tissue. The intraparenchymal transplantation of bone marrow mononuclear cells (BMMNCs) into liver tissue decreases aspartate aminotransferase (AST), alanine transaminase (ALT), bilirubin, CD34, and -SMA, suggesting that transplanted BMSCs restore hepatic functions through regeneration of hepatic tissues [113]. In order to meet the growing demand for stem cells transplantation therapy, donor encouragement is always required [8]. The stem cells donation procedure is very simple; with consent donor gets an injection of granulocyte-colony stimulating factor (G-CSF) that increases BMSCs population. Bone marrow collection is done from hip bone using syringe in 4-5hrs, requiring local anaesthesia and within a wk time frame donor gets recovered donation associated weakness.

The field of iPSCs technology and research is new to all other stem cells research, emerging in 2006 when, for the first time, Takahashi and Yamanaka generated ESCs-like cells through genetic incorporation of four factors, Sox2, Oct3/4, Klf4, and c-Myc, into skin fibroblast [3]. Due to extensive nuclear reprogramming, generated iPSCs are indistinguishable from ESCs, for their transcriptome profiling, epigenetic markings, and functional competence [3], but use of retrovirus in transdifferentiation approach has questioned iPSCs technology. Technological advancement has enabled generation of iPSCs from various kinds of adult cells phasing through ESCs or direct transdifferentiation. This section of review outlines most recent advancement in iPSC technology and regenerative applications (; ). Using the new edge of iPSCs technology, terminally differentiated skin cells directly can be transformed into kidney organoids [114], which are functionally and structurally similar to those of kidney tissue in vivo. Up to certain extent kidneys heal themselves; however natural regeneration potential cannot meet healing for severe injuries. During kidneys healing process, a progenitor stem cell needs to become 20 types of cells, required for waste excretion, pH regulation, and restoration of water and electrolytic ions. The procedure for generation of kidney organoids ex vivo, containing functional nephrons, has been identified for human. These ex vivo kidney organoids are similar to fetal first-trimester kidneys for their structure and physiology. Such kidney organoids can serve as model for nephrotoxicity screening of drugs, disease modelling, and organ transplantation. However generation of fully functional kidneys is a far seen event with today's scientific technologies [114]. Loss of neurons in age-related macular degeneration (ARMD) is the common cause of blindness. At preclinical level, transplantation of iPSCs derived neuronal progenitor cells (NPCs) in rat limits progression of disease through generation of 5-6 layers of photoreceptor nuclei, restoring visual acuity [78]. The various approaches of iPSCs mediated retinal regeneration including ARMD have been reviewed elsewhere [79]. Placenta, the cordial connection between mother and developing fetus, gets degenerated in certain pathophysiological conditions. Nuclear programming of OCT4 knock-out (KO) and wild type (WT) mice fibroblast through transient expression of GATA3, EOMES, TFAP2C, and +/ cMYC generates transgene independent trophoblast stem-like cells (iTSCs), which are highly similar to blastocyst derived TSCs for DNA methylation, H3K7ac, nucleosome deposition of H2A.X, and other epigenetic markings. Chimeric differentiation of iTSCs specifically gives rise to haemorrhagic lineages and placental tissue, bypassing pluripotency phase, opening an avenue for generation of fully functional placenta for human [115]. Neurodegenerative disease like Alzheimer's and obstinate epilepsies can degenerate cerebrum, controlling excitatory and inhibitory signals of the brain. The inhibitory tones in cerebral cortex and hippocampus are accounted by -amino butyric acid secreting (GABAergic) interneurons (INs). Loss of these neurons often leads to progressive neurodegeneration. Genomic integration of Ascl1, Dlx5, Foxg1, and Lhx6 to mice and human fibroblast transforms these adult cells into GABAergic-INs (iGABA-INs). These cells have molecular signature of telencephalic INs, release GABA, and show inhibition to host granule neuronal activity [81]. Transplantation of these INs in developing embryo cures from genetic and acquired seizures, where transplanted cells disperse and mature into functional neuronal circuits as local INs [82]. Dorsomorphin and SB-431542 mediated inhibition of TGF- and BMP signalling direct transformation of human iPSCs into cortical spheroids. These cortical spheroids consisted of both peripheral and cortical neurons, surrounded by astrocytes, displaying transcription profiling and electrophysiology similarity with developing fetal brain and mature neurons, respectively [83]. The underlying complex biology and lack of clear etiology and genetic reprogramming and difficulty in recapitulation of brain development have barred understanding of pathophysiology of autism spectrum disorder (ASD) and schizophrenia. 3D organoid cultures of ASD patient derived iPSC generate miniature brain organoid, resembling fetal brain few months after gestation. The idiopathic conditions of these organoids are similar with brain of ASD patients; both possess higher inhibitory GABAergic neurons with imbalanced neuronal connection. Furthermore these organoids express forkhead Box G1 (FOXG1) much higher than normal brain tissue, which explains that FOXG1 might be the leading cause of ASD [84]. Degeneration of other organs and tissues also has been reported, like degeneration of lungs which might occur due to tuberculosis infection, fibrosis, and cancer. The underlying etiology for lung degeneration can be explained through organoid culture. Coaxing of iPSC into inert biomaterial and defined culture leads to formation of lung organoids that consisted of epithelial and mesenchymal cells, which can survive in culture for months. These organoids are miniature lung, resemble tissues of large airways and alveoli, and can be used for lung developmental studies and screening of antituberculosis and anticancer drugs [87]. The conventional multistep reprogramming for iPSCs consumes months of time, while CRISPER-Cas9 system based episomal reprogramming system that combines two steps together enables generation of ESCs-like cells in less than twowks, reducing the chances of culture associated genetic abrasions and unwanted epigenetic [80]. This approach can yield single step ESCs-like cells in more personalized way from adults with retinal degradation and infants with severe immunodeficiency, involving correction for genetic mutation of OCT4 and DNMT3B [80]. The iPSCs expressing anti-CCR5-RNA, which can be differentiated into HIV1 resistant macrophages, have applications in AIDS therapeutics [88]. The diversified immunotherapeutic application of iPSCs has been reviewed elsewhere [89]. The -1 antitrypsin deficiency (A1AD) encoded by serpin peptidase inhibitor clade A member 1 (SERPINA1) protein synthesized in liver protects lungs from neutrophils elastase, the enzyme causing disruption of lungs connective tissue. A1AD deficiency is common cause of both lung and liver disease like chronic obstructive pulmonary disease (COPD) and liver cirrhosis. Patient specific iPSCs from lung and liver cells might explain pathophysiology of A1AD deficiency. COPD patient derived iPSCs show sensitivity to toxic drugs which explains that actual patient might be sensitive in similar fashion. It is known that A1AD deficiency is caused by single base pair mutation and correction of this mutation fixes the A1AD deficiency in hepatic-iPSCs [85]. The high order brain functions, like emotions, anxiety, sleep, depression, appetite, breathing heartbeats, and so forth, are regulated by serotonin neurons. Generation of serotonin neurons occurs prior to birth, which are postmitotic in their nature. Any sort of developmental defect and degeneration of serotonin neurons might lead to neuronal disorders like bipolar disorder, depression, and schizophrenia-like psychiatric conditions. Manipulation of Wnt signalling in human iPSCs in defined culture conditions leads to an in vitro differentiation of iPSCs to serotonin-like neurons. These iPSCs-neurons primarily localize to rhombomere 2-3 segment of rostral raphe nucleus, exhibit electrophysiological properties similar to serotonin neurons, express hydroxylase 2, the developmental marker, and release serotonin in dose and time dependent manner. Transplantation of these neurons might cure from schizophrenia, bipolar disorder, and other neuropathological conditions [116]. The iPSCs technology mediated somatic cell reprogramming of ventricular monocytes results in generation of cells, similar in morphology and functionality with PCs. SA note transplantation of PCs to large animals improves rhythmic heart functions. Pacemaker needs very reliable and robust performance so understanding of transformation process and site of transplantation are the critical aspect for therapeutic validation of iPSCs derived PCs [28]. Diabetes is a major health concern in modern world, and generation of -cells from adult tissue is challenging. Direct reprogramming of skin cells into pancreatic cells, bypassing pluripotency phase, can yield clinical grade -cells. This reprogramming strategy involves transformation of skin cells into definitive endodermal progenitors (cDE) and foregut like progenitor cells (cPF) intermediates and subsequent in vitro expansion of these intermediates to become pancreatic -cells (cPB). The first step is chemically complex and can be understood as nonepisomal reprogramming on day one with pluripotency factors (OCT4, SOX2, KLF4, and hair pin RNA against p53), then supplementation with GFs and chemical supplements on day seven (EGF, bFGF, CHIR, NECA, NaB, Par, and RG), and two weeks later (Activin-A, CHIR, NECA, NaB, and RG) yielding DE and cPF [86]. Transplantation of cPB yields into glucose stimulated secretion of insulin in diabetic mice defines that such cells can be explored for treatment of T1DM and T2DM in more personalized manner [86]. iPSCs represent underrated opportunities for drug industries and clinical research laboratories for development of therapeutics, but safety concerns might limit transplantation applications (; ) [117]. Transplantation of human iPSCs into mice gastrula leads to colonization and differentiation of cells into three germ layers, evidenced with clinical developmental fat measurements. The acceptance of human iPSCs by mice gastrula suggests that correct timing and appropriate reprogramming regime might delimit human mice species barrier. Using this fact of species barrier, generation of human organs in closely associated primates might be possible, which can be used for treatment of genetic factors governed disease at embryo level itself [118]. In summary, iPSCs are safe and effective for treatment of regenerative medicine.

The unstable growth of human population threatens the existence of wildlife, through overexploitation of natural habitats and illegal killing of wild animals, leading many species to face the fate of being endangered and go for extinction. For wildlife conservation, the concept of creation of frozen zoo involves preservation of gene pool and germ plasm from threatened and endangered species (). The frozen zoo tissue samples collection from dead or live animal can be DNA, sperms, eggs, embryos, gonads, skin, or any other tissue of the body [119]. Preserved tissue can be reprogrammed or transdifferentiated to become other types of tissues and cells, which opens an avenue for conservation of endangered species and resurrection of life (). The gonadal tissue from young individuals harbouring immature tissue can be matured in vivo and ex vivo for generation of functional gametes. Transplantation of SSCs to testis of male from the same different species can give rise to spermatozoa of donor cells [120], which might be used for IVF based captive breeding of wild animals. The most dangerous fact in wildlife conservation is low genetic diversity, too few reproductively capable animals which cannot maintain adequate genetic diversity in wild or captivity. Using the edge of iPSC technology, pluripotent stem cells can be generated from skin cells. For endangered drill, Mandrillus leucophaeus, and nearly extinct white rhinoceros, Ceratotherium simum cottoni, iPSC has been generated in 2011 [121]. The endangered animal drill (Mandrillus leucophaeus) is genetically very close to human and often suffers from diabetes, while rhinos are genetically far removed from other primates. The progress in iPSCs, from the human point of view, might be transformed for animal research for recapturing reproductive potential and health in wild animals. However, stem cells based interventions in wild animals are much more complex than classical conservation planning and biomedical research has to face. Conversion of iPSC into egg or sperm can open the door for generation of IVF based embryo; those might be transplanted in womb of live counterparts for propagation of population. Recently, iPSCs have been generated for snow leopard (Panthera uncia), native to mountain ranges of central Asia, which belongs to cat family; this breakthrough has raised the possibilities for cryopreservation of genetic material for future cloning and other assisted reproductive technology (ART) applications, for the conservation of cat species and biodiversity. Generation of leopard iPSCs has been achieved through retroviral-system based genomic integration of OCT4, SOX2, KLF4, cMYC, and NANOG. These iPSCs from snow leopard also open an avenue for further transformation of iPSCs into gametes [122]. The in vivo maturation of grafted tissue depends both on age and on hormonal status of donor tissue. These facts are equally applicable to accepting host. Ectopic xenografts of cryopreserved testis tissue from Indian spotted deer (Moschiola indica) to nude mice yielded generation of spermatocytes [123], suggesting that one-day procurement of functional sperm from premature tissue might become a general technique in wildlife conservation. In summary, tissue biopsies from dead or live animals can be used for generation of iPSCs and functional gametes; those can be used in assisted reproductive technology (ART) for wildlife conservation.

The spectacular progress in the field of stem cells research represents great scope of stem cells regenerative therapeutics. It can be estimated that by 2020 or so we will be able to produce wide array of tissue, organoid, and organs from adult stem cells. Inductions of pluripotency phenotypes in terminally differentiated adult cells have better therapeutic future than ESCs, due to least ethical constraints with adult cells. In the coming future, there might be new pharmaceutical compounds; those can activate tissue specific stem cells, promote stem cells to migrate to the side of tissue injury, and promote their differentiation to tissue specific cells. Except few countries, the ongoing financial and ethical hindrance on ESCs application in regenerative medicine have more chance for funding agencies to distribute funding for the least risky projects on UCSCs, BMSCs, and TSPSCs from biopsies. The existing stem cells therapeutics advancements are more experimental and high in cost; due to that application on broad scale is not feasible in current scenario. In the near future, the advancements of medical science presume using stem cells to treat cancer, muscles damage, autoimmune disease, and spinal cord injuries among a number of impairments and diseases. It is expected that stem cells therapies will bring considerable benefits to the patients suffering from wide range of injuries and disease. There is high optimism for use of BMSCs, TSPSCs, and iPSCs for treatment of various diseases to overcome the contradictions associated with ESCs. For advancement of translational application of stem cells, there is a need of clinical trials, which needs funding rejoinder from both public and private organizations. The critical evaluation of regulatory guidelines at each phase of clinical trial is a must to comprehend the success and efficacy in time frame.

Dr. Anuradha Reddy from Centre for Cellular and Molecular Biology Hyderabad and Mrs. Sarita Kumari from Department of Yoga Science, BU, Bhopal, India, are acknowledged for their critical suggestions and comments on paper.

There are no competing interests associated with this paper.

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Cardiac Stem Cells Comments Off on Stem Cells Applications in Regenerative Medicine and … | December 23rd, 2021

DUBLIN, Dec. 20, 2021 /PRNewswire/ -- The "22q11.2 Deletion Syndrome - Global Market Insights, Epidemiology and Forecast to 2030" report has been added to ResearchAndMarkets.com's offering.

This report delivers an in-depth understanding of the 22q11.2 deletion syndrome, historical and forecasted epidemiology as well as the 22q11.2 deletion syndrome market trends in the United States, EU5 (Germany, France, Italy, Spain, and the United Kingdom), and Japan.

Epidemiology

The 22q11.2 deletion syndrome epidemiology division provides the insights about historical and current 22q11.2 deletion syndrome patient pool and forecasted trend for each seven major countries. It helps to recognize the causes of current and forecasted trends by exploring numerous studies and views of key opinion leaders. This part of The report also provides the diagnosed patient pool and their trends along with assumptions undertaken.

Key Findings

The disease epidemiology covered in the report provides historical as well as forecasted 22q11.2 deletion syndrome epidemiology [segmented as Total Prevalent Cases of 22q11.2 deletion syndrome, Total Diagnosed Prevalent Cases of 22q11.2 deletion syndrome, Total diagnosed prevalent cases of 22q11.2 deletion syndrome by age group, Total diagnosed prevalent cases of 22q11.2 deletion syndrome with Behavioral and Psychiatric phenotypes, and Total treated cases of 22q11.2 deletion syndrome with behavioral and psychiatric phenotypes scenario of 22q11.2 deletion syndrome in the 7MM covering United States, EU5 countries (Germany, France, Italy, Spain, and United Kingdom), and Japan from 2018 to 2030.

Country-Wise Epidemiology

In 2020, the total prevalent cases of 22q11.2 deletion syndrome were 196,476 in the 7MM. The United States, in the same year, accounted for 83,326 cases, the highest prevalence of 22q11.2 deletion syndrome cases in the 7MM, accounting for approximately 42% of the total 7MM cases in 2020.

Among the EU-5 countries, the highest number of cases of 22q11.2 deletion syndrome were in Germany and the least in Spain in 2020.

22q11.2 deletion syndrome is often underdiagnosed and misdiagnosed, as the symptoms vary from patient to patient. In the EU-5 countries, the total diagnosed prevalent cases of 22q11.2 deletion syndrome were 35,203 in 2020.

In the year 2020, Japan accounted for 1,409, 1,160, 2,196, 582, and 850 cases for the age groups Infant, 1-5, 6-12, 13-17, and ?18 years, respectively, for 22q11.2 deletion syndrome which are expected to rise during the forecast period.

22q11.2 deletion syndrome is a multisystem disorder characterized by several physical, behavioral and psychiatric disorders. In the 7MM, of the focused age-group 6 to 12 and 13 to 17 years, the diagnosed prevalent cases of 22q11.2 deletion syndrome with Behavioral and Psychiatric Phenotypes were 36,702, in 2020.

Drug Chapters

Drug chapter segment of the 22q11.2 deletion syndrome report encloses the detailed analysis of 22q11.2 deletion syndrome pipeline drugs. It also helps to understand the 22q11.2 deletion syndrome clinical trial details, expressive pharmacological action, agreements and collaborations, approval and patent details, advantages and disadvantages of each included drug and the latest news and press releases.

Emerging Drugs

Zygel (ZYN002; Cannabidiol): Zynerba Pharmaceuticals

Zygel (ZYN002), developed by Zynerba Pharmaceuticals, is the first and only pharmaceutically produced Cannabidiol (CBD). Zygel is formulated as a patent-protected permeation-enhanced gel for transdermal delivery through skin and then into the circulatory system. Zynerba Pharmaceuticals is currently developing the Zygel in Phase II (ACTRN12619000673145; INSPIRE) of the clinical development in Children and Adolescents with 22q11.2 Deletion Syndrome. The trial is currently registered with the Australian New Zealand Clinical Trials Registry (ANZCTR).

RVT-802: Enzyvant/Roivant Sciences/Sumitomo Dainippon Pharma

RVT-802 is a one-time regenerative therapy and is a cultured human thymus tissue engineered to generate a functioning immune response when implanted in pediatric patients with congenital athymia. RVT-802 is a human thymus tissue that has been removed during pediatric cardiac surgery for unrelated conditions. In a healthy, functioning immune system, T cells that start as stem cells in the bone marrow become fully developed in the thymus. Currently, RVT-802 is being developed by Sumitomo Dainippon Pharma (Parent company of Sumitovant Biopharma for Pediatric Congenital Athymia) associated with multiple conditions, including complete DiGeorge Anomaly (cDGA).

Key Findings

The 22q11.2 deletion syndrome market size in the 7MM is expected to change during the forecast period (2021-2030), at a CAGR of 41.9%. According to the estimates, the highest market size of 22q11.2 deletion syndrome is found in the United States.

US: Market Outlook

In United States, the total market size of 22q11.2 deletion syndrome is expected to increase at a CAGR of 43.9% during the study period (2018-2030).

EU-5 Countries: Market Outlook

In the EU-5 countries, the total market size of 22q11.2 deletion syndrome is expected to increase at a CAGR of 37.1% during the study period (2018-2030).

Japan: Market Outlook

In the Japan, the total market size of 22q11.2 deletion syndrome is expected to increase at a CAGR of 41.6% during the study period (2018-2030).

Pipeline Activities

The drugs which are in pipeline include:

Analysts Insight

At present, like many other rare diseases, there is no cure for 22q11.2 deletion syndrome. It is worth mentioning that as a result of the early diagnosis in cases like heart and palate defects, evidence-based protocols can be followed in the early stages of diagnosis to improve the quality of life for children. In such cases, surgery is the major option. The major treatment challenge is seen in patients with psychopathologies (such as Autism, Anxiety disorders, Psychotic disorder [Schizophrenia], Attention deficit hyperactivity disorder [ADHD], and Mood Disorders). In such cases diagnosis is also a major challenge. Antidepressants, antipsychotics, and stimulants are used as off-label therapeutic choices to address all of the aforementioned behavioral and psychiatric traits. Behavioral therapy, on the other hand, is another important part of the treatment process. The pipeline for 22q11.2 deletion syndrome is not competitive, and if Zygel (ZYN002) gets approved by regulatory authorities in the coming years, the overall market size in the seven major markets is likely to grow, as there will be no expected competition.

Access and Reimbursement Scenario

Children are born with this disorder, they require a lifetime of expenditure over diagnosis, treatment, and other supportive care. In a study by Peter et al. (2017), the average pediatric medical care cost associated with the diagnosis of 22q11.2 deletion syndrome in the general population was estimated to be USD 727,178. Costs were highest for patients ascertained prenatally (USD 2,599,955) or in the first year of life (USD 1,043,096), those with cardiac abnormalities or referred for cardiac evaluation (USD 751,535), and patients with low T-cell counts (USD 1,382,222), presumably reflecting the fact that more severely affected cases are more likely to have come to attention early, and that they have a larger number of years of accumulated costs.

KOL Views

To keep up with current market trends, the publisher takes KOLs and SME's opinion working in 22q11.2 deletion syndrome domain through primary research to fill the data gaps and validate our secondary research. Their opinion helps to understand and validate current and emerging therapies treatment patterns o r22q11.2 deletion syndrome market trend. This will support the clients in potential upcoming novel treatment by identifying the overall scenario of the market and the unmet needs.

Competitive Intelligence Analysis

The publisher performs Competitive and Market Intelligence analysis of the 22q11.2 deletion syndrome Market by using various Competitive Intelligence tools that includes - SWOT analysis, PESTLE analysis, Porter's five forces, BCG Matrix, Market entry strategies etc. The inclusion of the analysis entirely depends upon the data availability.

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Original post:
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