CTERP INTERNATIONAL CONFERENCEApril 11-13, 2018Moscow, Russia

In recent years there have been rapid advances in applying the discoveries in cell technologies field into medical practice. Cell technologies are progressing as the result of multidisciplinary effort of scientists, clinicians and businessmen,with clinical applications of manipulated stem cells combining developments in transplantation and gene therapy.Challenges address not only thetechnology itself but also compliancewith safety and regulatory requirements.

The Conference will provide a platform for scientists from basic and applied cell biology fields, practical doctors, and biotech companies to meet and share their experience, to discuss the research associated with developing biomedical clinical products and translating this research into novel clinical applications, challenges of such translational efforts and foundation of bioclusters assisting further developments in cell technology.

The official language of the conference is English.

Conference materials will be published in the Russian Journal of Developmental Biology.

Please download your abstracts in accordance with the journal guidelines (english, russian) for authors provided on their website.

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CTERP International Conference - 2018: About

IPS Cell Therapy Comments Off on CTERP International Conference – 2018: About | January 4th, 2019

Bone marrow suppressionSynonymMyelotoxicity, myelosuppression

Bone marrow suppression also known as myelotoxicity or myelosuppression, is the decrease in production of cells responsible for providing immunity (leukocytes), carrying oxygen (erythrocytes), and/or those responsible for normal blood clotting (thrombocytes).[1] Bone marrow suppression is a serious side effect of chemotherapy and certain drugs affecting the immune system such as azathioprine.[2] The risk is especially high in cytotoxic chemotherapy for leukemia.

Nonsteroidal anti-inflammatory drugs (NSAIDs), in some rare instances, may also cause bone marrow suppression. The decrease in blood cell counts does not occur right at the start of chemotherapy because the drugs do not destroy the cells already in the bloodstream (these are not dividing rapidly). Instead, the drugs affect new blood cells that are being made by the bone marrow.[3] When myelosuppression is severe, it is called myeloablation.[4]

Many other drugs including common antibiotics may cause bone marrow suppression. Unlike chemotherapy the effects may not be due to direct destruction of stem cells but the results may be equally serious. The treatment may mirror that of chemotherapy-induced myelosuppression or may be to change to an alternate drug or to temporarily suspend treatment.

Because the bone marrow is the manufacturing center of blood cells, the suppression of bone marrow activity causes a deficiency of blood cells. This condition can rapidly lead to life-threatening infection, as the body cannot produce leukocytes in response to invading bacteria and viruses, as well as leading to anaemia due to a lack of red blood cells and spontaneous severe bleeding due to deficiency of platelets.

Parvovirus B19 inhibits erythropoiesis by lytically infecting RBC precursors in the bone marrow and is associated with a number of different diseases ranging from benign to severe. In immunocompromised patients, B19 infection may persist for months, leading to chronic anemia with B19 viremia due to chronic marrow suppression.[5]

Bone marrow suppression due to azathioprine can be treated by changing to another medication such as mycophenolate mofetil (for organ transplants) or other disease-modifying drugs in rheumatoid arthritis or Crohn's disease.

Bone marrow suppression due to anti-cancer chemotherapy is much harder to treat and often involves hospital admission, strict infection control, and aggressive use of intravenous antibiotics at the first sign of infection.[citation needed]

G-CSF is used clinically (see Neutropenia) but tests in mice suggest it may lead to bone loss.[6][7]

GM-CSF has been compared to G-CSF as a treatment of chemotherapy-induced myelosuppression/Neutropenia.[8]

In developing new chemotherapeutics, the efficacy of the drug against the disease is often balanced against the likely level of myelotoxicity the drug will cause. In-vitro colony forming cell (CFC) assays using normal human bone marrow grown in appropriate semi-solid media such as ColonyGEL have been shown to be useful in predicting the level of clinical myelotoxicity a certain compound might cause if administered to humans.[9] These predictive in-vitro assays reveal effects the administered compounds have on the bone marrow progenitor cells that produce the various mature cells in the blood and can be used to test the effects of single drugs or the effects of drugs administered in combination with others.

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Bone marrow suppression - Wikipedia

Bone Marrow Stem Cells Comments Off on Bone marrow suppression – Wikipedia | January 3rd, 2019

A bone marrow transplant, also called a stem cell transplant, is a treatment for some types of cancer. For example, you might have one if you have leukemia, multiple myeloma, or some types of lymphoma. Doctors also treat some blood diseases with stem cell transplants.

In the past, a stem cell transplant was more commonly called a bone marrow transplant because the stem cells were collected from the bone marrow. Today, stem cells are usually collected from the blood, instead of the bone marrow. For this reason, they are now often called stem cell transplants.

A part of your bones called bone marrow makes blood cells. Marrow is the soft, spongy tissue inside bones. It contains cells called hematopoietic stem cells (pronounced he-mah-tuh-poy-ET-ick). These cells can turn into several other types of cells. They can turn into more bone marrow cells. Or they can turn into any type of blood cell.

Certain cancers and other diseases keep hematopoietic stem cells from developing normally. If they are not normal, neither are the blood cells that they make. A stem cell transplant gives you new stem cells. The new stem cells can make new, healthy blood cells.

The main types of stem cell transplants and other options are discussed below.

Autologous transplant. This is also called an AUTO transplant or high-dose chemotherapy with autologous stem cell rescue.

In an AUTO transplant, you get your own stem cells after doctors treat the cancer. First, your health care team collects stem cells from your blood and freezes them. Next, you have powerful chemotherapy, and rarely, radiation therapy. Then, your health care team thaws your frozen stem cells. They put them back in your blood through a tube placed in a vein (IV).

It takes about 24 hours for your stem cells to reach the bone marrow. Then they start to grow, multiply, and help the marrow make healthy blood cells again.

Allogeneic transplantation. This is also called an ALLO transplant.In an ALLO transplant, you get another persons stem cells. It is important to find someone whose bone marrow matches yours. This is because you have certain proteins on your white blood cells called human leukocyte antigens (HLA). The best donor has HLA proteins as much like yours as possible.

Matching proteins make a serious condition called graft-versus-host disease (GVHD) less likely. In GVHD, healthy cells from the transplant attack your cells. A brother or sister may be the best match. But another family member or volunteer may also work.

Once you find a donor, you receive chemotherapy with or without radiation therapy. Next, you get the other persons stem cells through a tube placed in a vein (IV). The cells in an ALLO transplant are not typically frozen. This way, your doctor can give you the cells as soon as possible after chemotherapy or radiation therapy.

There are 2 types of ALLO transplants. The best type for each person depends on his or her age, health, and the type of disease being treated.

Ablative, which uses high-dose chemotherapy

Reduced intensity, which uses milder doses of chemotherapy

If your health care team cannot find a matched adult donor, there are other options. Research is ongoing to determine which type of transplant will work best for different people.

Umbilical cord blood transplant. This may be an option if you cannot find a donor match. Cancer centers around the world use cord blood.

Parent-child transplant and haplotype mismatched transplant. These types of transplants are being used more often. The match is 50%, instead of near 100%. Your donor might be a parent, child, brother, or sister.

Your doctor will recommend an AUTO or ALLO transplant based mostly on the disease you have. Other factors include the health of your bone marrow and your age and general health. For example, if you have cancer or other disease in your bone marrow, you will probably have an ALLO transplant. In this situation, doctors do not recommend using your own stem cells.

Choosing a transplant is complicated. You will need help from a doctor who specializes in transplants. You might need to travel to a center that does many stem cell transplants. Your donor might also need to go. At the center, you will talk with a transplant specialist and have an examination and medical tests.

Before a transplant, you should also think about non-medical factors. These include:

Who can care for you during treatment

How long you will be away from work and family responsibilities

If your insurance pays for the transplant

Who can take you to transplant appointments

Your health care team can help you find answers to these questions.

The information below tells you the main parts of AUTO and ALLO transplants. Your health care team usually does the steps in order. But sometimes certain steps happen in advance, such as collecting stem cells. Ask your health care team what to expect before, during, and after a transplant.

Part 1: Collecting your stem cells

During this part, you get injections of a medication to raise your number of stem cells.Your doctor may collect stem cells through your veins using standard IVs or a catheter, which is placed in a large vein in the chest. This stays in place throughout your stay at the hospital. The catheter is used to give chemotherapy, other medications, and blood transfusions.

Time: Several days

Where it is done: Clinic or hospital building. You do not need to stay in the hospital overnight.

Part 2: Transplant treatment

You get high doses of chemotherapy, and rarely, radiation therapy.

Time: 5 to 10 days

Where it is done: A clinic or hospital. At many transplant centers, people need to stay in the hospital for the duration of the transplant, usually about 3 weeks. At some centers, a person receives treatment in the clinic and can come in every day.

Part 3: Getting your stem cells back

This part is called the stem cell infusion. Your health care team puts your stem cells back in your blood through the transplant catheter.

Time: Each infusion usually takes less than 30 minutes. You may receive more than 1 infusion.

Where it is done: A clinic or hospital.

Part 4: Recovery

You take antibiotics and other drugs. You get blood transfusions through your transplant catheter, if needed. This is also when your health care team helps with any transplant side effects.

Time: Approximately 2 weeks

Where it is done: A clinic or hospital. You might be staying in the hospital.

Part 1: Collecting stem cells from your donor

During this part, the health care team gives your donor injections of a medication to increase white cells in the blood, if the cells are collected from blood. Some donors will donate bone marrow in the operating room during a procedure which takes several hours.

Time: Varies based on how the stem cells are collected

Where it is done: A clinic or hospital

Part 2: Transplant treatment

You get chemotherapy with or without radiation therapy.

Time: 5 to 7 days

Where it is done: Many ALLO transplants are done in the hospital.

Part 3: Getting the donor cells

This part is called the stem cell infusion. Your health care team puts the donors stem cells in your blood through the transplant catheter. It takes less than 1 hour. The transplant catheter stays in until after treatment.

Time: 1 day

Where it is done: A clinic or hospital

Part 4: Recovery

During the recovery, you receive antibiotics and other drugs. This includes medications to prevent graft-versus-host disease. If needed, you get blood transfusions through your catheter. This is also when your health care team takes care of any side effects from the transplant.

After the transplant, people visit the clinic frequently at first and less often over time.

Time: It varies.For an ablative transplant, people are usually in the hospital for about 4 weeks in total.For a reduced intensity transplant, people are in the hospital or visit the clinic daily for about a week.

The words successful transplant might mean different things to you, your family, and your health care team. Below are 2 ways to measure transplant success: Your blood counts are back to safe levels. A blood count is the number of red cells, white cells, and platelets in your blood. A transplant makes these numbers very low for 1 to 2 weeks. This causes risks of:

Infection from low numbers of white cells, which fight infections

Bleeding from low numbers of platelets, which stop bleeding

Tiredness from low numbers of red cells, which carry oxygen

Doctors lower these risks by giving blood and platelet transfusions after a transplant. You also take antibiotics to help prevent infections. When the new stem cells multiply, they make more blood cells. Then your blood counts improve. This is one way to know if a transplant is a success.

It controls your cancer. Doctors do stem cell transplants with the goal of curing disease. A cure may be possible for some cancers, such as some types of leukemia and lymphoma. For other people, remission is the best result. Remission is having no signs or symptoms of cancer. After a transplant, you need to see your doctor and have tests to watch for any signs of cancer or complications from the transplant.

Talking often with your health care team is important. It gives you information to make decisions about your treatment and care. The following questions may help you learn more about stem cell transplant:

Which type of stem cell transplant would you recommend? Why?

If I will have an ALLO transplant, how will we find a donor? What is the chance of a good match?

What type of treatment will I have before the transplant? Will radiation therapy be used?

How long will my treatment take? How long will I stay in the hospital?

How will a transplant affect my life? Can I work? Can I exercise and do regular activities?

How will we know if the transplant works?

What if the transplant does not work? What if the cancer comes back?

What are the short-term side effects that may happen during treatment or shortly after?

What are the long-term side effects that may happen years later?

What tests will I need later? How often will I need them?

If I am worried about managing the costs of treatment, who can help me with these concerns?

Side Effects of a Bone Marrow Transplant (Stem Cell Transplant)

Bone Marrow Aspiration and Biopsy

Donating Bone Marrow is Easy and Important: Here's Why

How Umbilical Cord BloodCan Save Someone's Life

Bone Marrow Transplants and Older Adults: 3 Important Questions

Be the Match: About Transplant

Be the Match: National Marrow Donor Program

Blood & Marrow Transplant Information Network (BMT InfoNet) National Bone Marrow Transplant Link (nbmtLINK)

U.S. Department of Health and Human Services: Learn About Transplant as a Treatment Option

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What is a Bone Marrow Transplant (Stem Cell Transplant ...

Bone Marrow Stem Cells Comments Off on What is a Bone Marrow Transplant (Stem Cell Transplant … | December 30th, 2018

Injury to the spinal cord can be caused by acute (sudden) or chronic (developing) trauma as well as medical conditions. Frequent causes of chronic compression injuries are herniated disks and primary or secondary tumors. Compromised blood perfusion, the delivery of nutritive arterial blood to capillary bed, as in anterior spinal cord syndrome can also be severely detrimental to spinal cord function. However the most damaging Spinal Cord Injury is one of acute trauma resulting in permanent paralysis.

Traumatic spinal cord injury have been classified into five categories by the American Spinal Injury Association and the International Spinal Cord Injury Classification System:

Spinal cord injury where no motor or sensory function remains in the sacral segments S4-S5.

Spinal cord injury sensory but not motor function remains below the neurological level and includes the sacral segments S4-S5. Typically a transient phase and if the person recovers any motor function below the neurological level, theyare considered motor incomplete and classified C or D.

Spinal cord injury where motor function remains below the neurological level and more than half of key muscles below the neurological level have a muscle grade of less than 3, which indicates active movement with full range of motion against gravity.

Spinal cord injury where motor function exists below the neurological level and at least half of the key muscles below the neurological level have a muscle grade of 3 or more.

Where motor and sensory scores are normal. It is possible to have spinal cord injury and neurological deficits with completely normal motor and sensory scores.

The annual incidence rate of spinal cord injury varies from country to country, ranging from 15 to 71 per million (/m). In 2008 the incidence of spinal cord injury in the United Kingdom around 13 /m, Australia 14 /m, Canadi 35 /m, China 65 /m and the United States 35 /m per year. This suggests around 40 per million or 52,000 spinal injuries occur every year globally.

Of the 12,000 new cases of paraplegia and quadriplegia that occur in the United States each year 4,000 patients die before reaching hospital. Causes of acute spinal cord injury include motor vehicle accidents, work-related accidents, recreational accidents, falls and violence (shootings and stab wounds).

Paralysis occurs our times as often in males as females where about 60% of victims are under 30 years of age and 5% under 13 years of age (the pediatric age group). Falls from a height greater than their own is the largest cause of spinal trauma amongst the pediatric age group. A long-term outcome study of patients aged 25 to 34 who had suffered acute traumatic SCI before the pediatric age showed an employment rate of 54% while the employment rate in the general population for the same age group was 84%.

Limitation or complete loss of the capability to achieve economic independence following SCI combined with additional medical costs causes severe economic hardship for many living with paralysis and their immediate family. Further limitations to living a full social life are architectural barriers, buildings only accessible by stairs and a lack of ramps on sidewalks for example.

Increased awareness through education has played a key role in resolving these barriers and those created by negative or overprotective attitudes of healthy, non-injured people toward persons with spinal cord injury. When persons with spinal cord injury cannot fully participate society suffers. Not only are ethical standards, artistic and financial contributions to society lost, huge expenses for specialised lifelong care are incurred.

80% of SCI occur in people under the age of 30. The average life-time cost of thoracic paraplegia is $1.25 million and high level cervical quadriplegia such as those on ventilators $25 million USD. In 1990 the cost for acute and long term care of surviving spinal cord injury victims was estimated at $4 billion in the United States alone.

Road traffic accidents 45%

Domestic and industrial accidents 34%

Sporting injuries 15%

Self harm and criminal assault 6%

The first known description of acute spinal cord trauma and resulting neurological deficits was in the Edwin Smith papyrus which is believed to be more than 3,500 years old. In this ancient Egyptian document Smith accurately described the clinical symptoms and traumatic effects of quadriplegia (tetraplegia) anailment not to be treated. An indication of the feelings helplessness medical practitioners suffered at the time, a doctors value measured by the extent of cure achieved.

No strategies ensuring longterm survival for patients with spinal cord injury existed. A view which prevailed well into the early 1900s. In the First World War the mortality rate for those with a spinal cord injury was 95%, mainly attributed to urinary sepsis and complications from pressure sores. Less than 1% survived for more than twenty years.

During World War II the number of casualties from spinal cord injuries both military and civilian increased dramatically in Europe. Specialized hospital units known as peripheral nerve centers developed between the wars in Germany and the United States demonstrating the advantages of concentrating special needs patients under specialized care. Great importance was placed on the unique opportunities offered by these specialized units. Gaining new insight in the natural course of the disease and further development of new therapeutic strategies.

Building on those experiences, specialized spinal cord injury units started opening throughout England in the 1940s. Mortality rates from a spinal cord injury were recorded at 35% in the 1960s. Today nearly every capital city operates an acute care spinal unit.

Dr. Ludwig Guttmann and his colleagues at the Spinal Cord Unit of Stoke Mandeville Hospital developed new treatment approaches including frequent repositioning of paralyzed patients to avoid developing bedsores, a potential source of sepsis and intermittent sterile catheterization to prevent urinary sepsis. The success in patient survival was dramatic enough to require development of completely new strategies for social reintegration of patients with spinal cord injury. Adapted workplaces and wheelchair accessible housing championed in the 1940s and 1950s by the English Red Cross has today become an integral component in the framework of social politics in most industrialized countries. Respiratory complications are now the leading cause of death in patients admitted with SCI. Secondary are heart disease, septicemia (blood poisoning), pulmonary emboli (blood clot in lungs), suicide, and unintentional injuries.

Dr. Guttmann and his colleagues viewed physical rehabilitation as the basis of social reintegration both physically and psychologically. Supporting the idea of athletic competition in disciplines adequate and adapted to the physical capacity of their patients. Starting with two teams a competition in 1948 paralleling the Olympic Games in England, the idea of competitive sports for the paralyzed developed rapidly.

In 1960 the first Paralympic Games were held in Rome. The Paralympic games were held in the same year as the Olympic Games for the able-bodied using the same facilities, a tradition that has been followed ever since. The idea of competitive sports was extended to include people with a multitude of physical handicaps other than spinal cord injury emerging as the Paralympics we know today.

In many countries initiatives have risen at communal and national levels with the intent to decrease the incidence of spinal cord trauma and offer support and advice to both those with spinal cord injuries and their families. Many generously offer financial support for scientific and clinical research.

The prevention oriented Think First initiative, Canadian-based CORD and Wheels in Motion, the Christopher Reeve Paralysis Foundation, the U.K. Spinal Cord Trust, and the Paralyzed Veterans of America all maintain informative web sites with valuable information on the subject of spinal cord injury.

Although the overall incidence of SCI has not noticeably decreased the severity of injuries has deceased overall. Fewer now suffer complete injuries and survival rates have increased. This is mostly attributed to improvements in prehospital care including widespread instruction of first aid principles as well as the introduction of spinal cord immobilization and administration of advanced medicines during rescue and transport. Increased public awareness of risk factors leading to head trauma and spinal cord injury, the introduction of mandatory use of safety belts and installation of air bags in modern vehicles has also served to decrease trauma severity.

Until recently research suggested once spinal cord trauma had occurred nothing could be done to alter the natural course of developing pathology, that damage to the central nervous system was permanent and repair impossible. At the beginning of the twenty-first century this belief came to change in the minds of scientists, clinicians, patients and their families. Research laboratories around the world adopted two new approaches:

1. Prevention of secondary injury and repair of manifest damage. The term secondary injury describes the observation that central nervous system structures that survived the primary mechanical trauma die at a later point in time due to deterioration of the milieu (nerve ending sheath) at the site of injury.

2. The amount and severity of secondary injury damage can be significantly larger than that of the primary injury. Researchers focused on identification of substances and therapeutic methods that help minimize secondary injury effects. In the field of cell biology, isolation and manipulation of specific cell types is being undertaken in effort to induce certain cell types, including stem cells and olfactory ensheathing cells to help repair damaged central nervous system structures.

Clinical research continues to improve outcomes for those with a spinal cord injury, such as stimulators for bladder control, orthopedic correctional procedures and physical mobilization. Integration of biomedical research like pattern generators, mechanics and kinetics of movement with the latest developments in computer science and engineering has given rise to neuronal networks. Neuroprostheses are being developed which enable paraplegics to move about and walk.

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Spinal Cord Injury Explained - Mad Spaz Club

Spinal Cord Stem Cells Comments Off on Spinal Cord Injury Explained – Mad Spaz Club | December 25th, 2018

Mayo Clinic is enrolling patients in a phase 1 clinical trial of adipose stem cell treatment for spinal cord injury caused by trauma. The researchers already have approval from the Food and Drug Administration for subsequent phase 2A and 2B randomized control crossover trials.

Participants in the phase 1 clinical trial must have experienced a trauma-related spinal cord injury from two weeks to one year prior to enrollment. They will receive intrathecal injections of adipose-derived mesenchymal stem cells. No surgery or implantable medical device is required.

"That is the most encouraging part of this study," says Mohamad Bydon, M.D., a consultant in Neurosurgery specializing in spinal surgery at Mayo Clinic in Rochester, Minnesota, and the study's director. "Intrathecal injection is a well-tolerated and common procedure. Stem cells can be delivered with an implantable device, but that would require surgery for implantation and additional surgeries to maintain the device. If intrathecal treatment is successful, it could impact patients' lives without having them undergo additional surgery or maintain permanently implantable devices for the rest of their lives."

To qualify for the trial, patients must have a spinal cord injury of grade A or B on the American Spinal Injury Association (ASIA) Impairment Scale. After evaluation at Mayo Clinic, eligible patients who enroll will have adipose tissue extracted from their abdomens or thighs. The tissue will be processed in the Human Cellular Therapies Laboratories, which are co-directed by Allan B. Dietz, Ph.D., to isolate and expand stem cells.

Four to six weeks after the tissue extraction, patients will return to Mayo Clinic for intrathecal injection of the stem cells. The trial participants will then be evaluated periodically for 96 weeks.

Mayo Clinic has already demonstrated the safety of intrathecal autologous adipose-derived stem cells for neurodegenerative disease. In a previous phase 1 clinical trial, with results published in the Nov. 22, 2016, issue of Neurology, Mayo Clinic researchers found that therapy was safe for people with amyotrophic lateral sclerosis (ALS). The therapy, developed in the Regenerative Neurobiology Laboratory under the direction of Anthony J. Windebank, M.D., is moving into phase 2 clinical trials.

Dr. Windebank is also involved in the new clinical trial for people with traumatic spinal cord injuries. "We have demonstrated that stem cell therapy is safe in people with ALS. That allows us to study this novel therapy in a different population of patients," he says. "Spinal cord injury is devastating, and it generally affects people in their 20s or 30s. We hope eventually that this novel therapy will reduce inflammation and also promote some regeneration of nerve fibers in the spinal cord to improve function."

Mayo Clinic's extensive experience with stem cell research provides important guidance for the new trial. "We know from prior studies that stem cell treatment can be effective in aiding with regeneration after spinal cord injury, but many questions remain unanswered," Dr. Bydon says. "Timing of treatment, frequency of treatment, mode of delivery, and number and type of stem cells are all open questions. Our hope is that this study can help answer some of these questions."

In addition to experience, Mayo Clinic brings to this clinical trial the strength of its multidisciplinary focus. The principal investigator, Wenchun Qu, M.D., M.S., Ph.D., is a consultant in Physical Medicine and Rehabilitation at Mayo Clinic's Minnesota campus, as is another of the trial's investigators, Ronald K. Reeves, M.D. Dr. Dietz, the study's sponsor, is a transfusion medicine specialist. Also involved is Nicolas N. Madigan, M.B., B.Ch., BAO, Ph.D., a consultant in Neurology at Mayo Clinic's Minnesota campus.

The study team is in discussions with U.S. military medical centers to enroll patients, and discussing additional collaboration with international sites, potentially in Israel or Europe, for future phases of the study.

"At Mayo Clinic, we have a high-volume, patient-centered multidisciplinary practice," Dr. Bydon says. "That allows us to do the most rigorous scientific trial that is in the best interests of our patients."

Mayo Clinic. Adipose Stem Cells for Traumatic Spinal Cord Injury (CELLTOP). ClinicalTrials.gov.

Staff NP, et al. Safety of intrathecal autologous adipose-derived mesenchymal stromal cells in patients with ALS. Neurology. 2016;87:2230.

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Clinical trial of stem cell therapy for traumatic spinal ...

Spinal Cord Stem Cells Comments Off on Clinical trial of stem cell therapy for traumatic spinal … | December 24th, 2018

Stem Cell Therapy for Spinal Cord Injury-Spinal cord injury is one of the progressively degenerating, crippling disorders attributing towards the dislocation of bones and vertebrae; which is a general result of trauma and/or injury.

The accidental injury generally damages connecting nerves internally; in order to halt the back and forth communication between brain and rest of the body parts. This communication gap is the primary cause of partial or complete loss of movement, paralysis as well as numbness. Apparently, many times it has also been evident that spinal cord may get affected not because of the injury but because of different types of nerve infection; which if ignored for a longer time, may allow unusual bleeding in between the spaces around the spinal cord. Some of the common forms of these notable infections are spinal stenosis, spina bifida, etc.

A person with a potential threat to severe spinal cord damage should be hospitalized for an intensive care unit immediately. Stabilization of blood pressure, lung function, and prevention of further damage to the spinal cord; should be emphasized with immediate effect. Other injuries are as well to be looked at; for an accidental damage.

Experts may prescribe some routine tests, in order to detect the extent of injuries. These tests can be

Classification of SCI is generally based on the extent of pain and loss of movement, associated with the damage. Moreover, when the damage is associated with neuronal loss, nerve locations and anumber of nerves that have been damaged can as well be referred to classify spinal cord injury.

The recovery period for patients suffering from spinal cord injury is dependent upon the level of injury, muscular strength and the type of injury; but in general, the notable recovery period can be anytime between 4-6 months.

Through conventionally demonstrated medicines, it is generally impossible to completely cure spinal cord damage or paralytic aftereffects of injury. In fact, the anti-inflammatory medicines that have been prescribed conventionally can affect other vital organs of the body, due to continuous hormonal modifications. Although with the advent of stem cells through the science of regenerative medicine has proven to be very helpful in offering a definite cure for SCI and other orthopedic related illnesses. The potential ability of these stem cells to be differentiated into neurons has been well studied and confirmed through different scientific literature and the same hypothesis can be applied to treat and restore back the functional attributes of damaged spinal cord.

Thus, stem cells and their regenerative powers can potentially work to solve the internal mysteries of spinal cord injury; but the extent of recovery and therapeutic outcome are still the challenges that are being faced by the medical fraternities.

For further queries regardingstem cell therapy for spinal cord injury, feel free to connect us at+91-96543 21400 or info@advancells.com. You can also connect us through Advancells Enquiry.

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Stem Cell Therapy for Spinal Cord Injury- Treatment for ...

Spinal Cord Stem Cells Comments Off on Stem Cell Therapy for Spinal Cord Injury- Treatment for … | December 23rd, 2018

Theme Leaders

James Martin, M.D. Ph.D.Professor, Molecular PhysiologyResearch Interest - Hippo, Wnt, Bmp signaling in development, regeneration, heart disease

Todd Rosengart, M.D., F.A.C.S.Chair/Professor, SurgeryResearch Interest - Cardiac regeneration, cardiac gene therapy, angiogenesis

Members of Theme Six are developing stem cell and cellular reprogramming strategies to treat cardiovascular diseases such as infarction in situ. The goal is to use viral vectors to induce transdifferentiation of cardiac fibroblasts and myofibroblasts into functionalcardiomyocytes in situ in a patients heart. We are modeling and developing the processes in rats, pigs, and in human cardiac fibroblasts. The hope is to have options available for clinical trials within 3-5 years.

Members of Theme Six are involved in research aimed at improving heart function after different types of injury and in particular the devastating loss of heart muscle after myocardial infarction. One current approach is to investigate gene pathways, many of which are important in heart development, that enhance the ability of cardiac muscle to respond to injury. Recent exciting findings have shown that manipulations of specific genetic pathways, such as the Hippo pathway, enhance heart repair. Current investigations in this area include uncovering the molecular mechanisms underlying improved heart repair in order to develop novel therapies.

Another exciting approach involves in vivo reprogramming of cardiac fibroblasts into cardiac muscle as a way to enhance heart function after ischemic injury. This novel method was inspired by the observation by Yamanaka that fibroblasts can be reprogrammed to pluripotent cells in cultured cells. Important recent work has shown that providing a cocktail of factors to cardiac fibroblasts results in conversion of those fibroblasts into cardiac muscle. Current efforts are directed at improving the efficiency of in vivo reprogramming with the goal of using this approach in therapy, recognizing that use of this strategy in human cells will likely be more challenging than in rodent and other non-human strains. The combination of angiogenic pretreatment of scar with this strategy appears to be critical to its success.

Sadek HA, Martin JF, Takeuchi JK, Leor J, Nei Y, Giacca M, Lee RT. Multi-investigator letter on reproducibility of neonatal heart regeneration following apical resection. Stem Cell Reports. 2014; 3(1): 1.

Yen ST, Zhang M, Deng JM, Usman SJ, Smith CN, Parker-Thornburg J, Swinton PG, Martin JF, Behringer RR. Somatic mosaicism and allele complexity induced by CRISPR/Cas9 RNA injections in mouse zygotes. Dev Biol. 2014; 393(1): 3-9.

C. Thomas Caskey, M.D. - FACP, FRSC Schizophrenia disease genes

Katarzyna Cieslik, Ph.D. - Cardiac mesenchymal progenitors

Austin Cooney, Ph.D. - Nuclear receptor regulation of embryonic stem cell function

Thomas Cooper, M.D. - Alternative splicing in cardiac development and disease

Mary Dickinson, Ph.D. - Role of fluid-derived mechanical forces in vascular remodeling and heart morphogenesis

Mark Entman, M.D. - Molecular mechanisms of cardiac injury and repair, inflammatory signaling

Charles Fraser, M.D. - Congenital heart surgery outcomes, bioengineering and assist devices

Peggy Goodell, M.D. - Hematopoietic stem cells, epigenetic modifications

Jeffrey Jacot, Ph.D. - Regenerative therapies for congenital heart disease

Sandra Haudek, Ph.D. - Circulating monocytic fibroblast precursors, cardiac hypertrophy

George Noon, M.D. - Transplant and assist devices

JoAnn Trial, Ph.D. - Origins of fibroblasts in cardiac injury healing

Peter Tsai, M.D., FACS - Custom-fenestrated endovascular stents to repair aortic transections or aneurysms

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Cardiac Regeneration, Stem Cells | Research | Baylor ...

Cardiac Stem Cells Comments Off on Cardiac Regeneration, Stem Cells | Research | Baylor … | December 23rd, 2018

Preclinical Research

Scientists are developing novel therapeutics for the treatment of cardiovascular diseases using cardiac-derived stem cells in mice and large-animal models. Three current projects are studying:

ExosomesOur researchers are isolating exosomes from specialized human cardiac-derived stem cells and finding that they have the same beneficial effects as other types of stem cells. In mice models, our research shows that exosomes produce the same post-surgery benefits, such as decreasing scar size, increasing healthy heart tissue and reducing levels of chemicals that lead to inflammation. This research suggests that exosomes convey messages that reduce cell death, promote growth of new heart muscle cells and encourage the development of healthy blood vessels.

Mechanisms of Heart Regeneration by Cardiosphere-Derived CellsInvestigators seek to understand the basic mechanisms of coronary artery disease in preclinical disease models. We hope to gather novel mechanistic insights, enabling us to boost the efficacy of stem cell-based treatments by bolstering the regeneration of injured heart muscle.

Biological PacemakersUsing an engineered virus carrying T-box (TBx18), Cedars-Sinai researchers are reprogramming heart muscle cells (cardiomyoctes) into induced sinoatrial node cells in pigs. Cedars-Sinai research shows that these new cells generate electrical impulses spontaneously and are indistinguishable from sinoatrial node or native pacemaker cells. Investigators believe this could be a viable therapeutic avenue for pacemaker-dependent patients afflicted with device-related complications.

Researchers hope to someday incorporate therapeutic regeneration as a regular treatment option for a broad range of cardiovascular disorders, such as myocardial infarctions, heart failure, refractory angina and peripheral vascular disease. Through the Regenerative Medicine Clinic at the Cedars-Sinai Heart Institute, several cardiac stem cell trials are underway. They include:

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Cardiac Stem Cells - Cedars-Sinai

Cardiac Stem Cells Comments Off on Cardiac Stem Cells – Cedars-Sinai | December 20th, 2018

Laura Dominguez-Tauer is a living, breathing example of what it takes to overcome adversity. An oil spill on a San Antonio freeway is blamed for the car crash that sent Laura and her brother directly into a retaining wall in 2001. As she lay tangled in the middle of the car, she heard a paramedic say, get a neck brace, she has a broken neck.

I didnt feel anything. I couldnt move my arms, I couldnt move my hands,

Laura was paralyzed from the neck down. I didnt feel anything. I couldnt move my arms, I couldnt move my hands, Laura said.

While others might have given up, Laura and her family started immediately searching for answers. They learned about adult stem cells and the promising results for spinal cord injury patients. In 2010, Laura joined a handful of other spinal cord patients and received an adult stem cell transplant. The transplant was a success.

Laura says, Before the stem cell procedure, I wasnt able to move very much. And then after the procedure Im able to get up. Im able to stand and walk around a little bit with help. The stem cell procedure made my upper body a lot stronger. I can feel my entire body now.

Laura went to work making herself stronger. Through physical therapy and a lot of hard work, she grew stronger and stronger. Instead of feeling sorry for herself, she opened a gym called Beyond the Chair. We opened Beyond the Chair to help people with any type of neurological disability whether its spinal cord injury, traumatic brain injury, strokes. We dont turn anybody away. Were going to help people.

In 2010, she met a young man, fell in love and was married. Then came a big surprise. I found out I was pregnant in April of 2016 and I was in disbelief, says Laura. We heard his heartbeat for the first time, and it was kind of like, oh my gosh, this is such a dream come true, its a miracle.

Young Joshau, named after his father, is what Laura is focused on now. She still helps run Beyond the Chair, but her days are mostly spent being a mom and promoting adult stem cell research.

Says Laura, a lot of people ask me about my experience with stem cells. I always tell them that at the end of the day the decision is up to them. But I promote them, I believe in them, I experienced it.

I think having the adult stem cell procedure was the best decision that Ive ever made.(Quote) I think that its been very beneficial, its helped me out so much, Laura said. My hope is that I can help other people and encourage other people. And spread the word about adult stem cells.

Disclaimer: StemCellResearchFacts.org is committed to educate about adult stem cell clinical trials and treatments which are validated by published research and approved by the U.S. FDA or similar international agencies. Clinical trials may not be effective for all patients or conditions. We are not a research or clinical facility and do not provide clinical trials or treatments.

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A stem cell or bone marrow transplant replaces damaged blood cells with healthy ones. It can be used to treat conditions affecting the blood cells, such as leukaemia and lymphoma.

Stem cells arespecial cells produced bybone marrow (aspongytissue found in the centre of some bones) that can turn into different types of blood cells.

The 3 maintypes of blood cellthey can become are:

A stem cell transplant involves destroying any unhealthy blood cells and replacing them with stem cells removed from the blood or bone marrow.

Stem cell transplants are used to treat conditions in which the bone marrow is damaged and is no longer able to produce healthy blood cells.

Transplants can also be carried out to replace blood cells that are damaged or destroyed as a result of intensive cancer treatment.

Conditions that stem cell transplants can be used to treat include:

A stem cell transplant will usually only be carried out if other treatments haven't helped, the potential benefits of a transplant outweigh the risks and you're in relatively good health, despite your underlying condition.

A stem cell transplant can involve taking healthy stem cells from the blood or bone marrow of one person ideally a close family member with the same or similar tissue type (see below) and transferring them to another person. This is called an allogeneic transplant.

It's also possible to remove stem cells from your own body and transplant them later, after any damaged or diseased cells have been removed. This is called an autologous transplant.

Astem celltransplant has 5 main stages. These are:

Having a stem cell transplant can be an intensive and challenging experience. You'll usually need to stay in hospital fora month or more until the transplant starts to take effect and itcan takea year or 2 to fully recover.

Read more about what happens during a stem cell transplant.

Stem celltransplants arecomplicated procedures with significant risks. It's important that you're aware of both the risks and possible benefits before treatment begins.

Possible problems that can occur during or after the transplant process include:

Read more about the risks of having a stem cell transplant.

Ifit isn't possible to use your own stem cells for the transplant (see above), stem cells will need to come from a donor.

To improve the chances ofthetransplant being successful, donated stem cells need tocarry a special genetic marker known as a human leukocyte antigen (HLA) that'sidentical or very similar to that of the person receiving the transplant.

The best chance of getting a match is from a brother or sister, or sometimes another close family member. If there are no matches in your close family,a search of theBritish Bone Marrow Registry will be carried out.

Most peoplewill eventually find a donor in the registry,although a small number of people may find it very hard or impossibleto find a suitable match.

The NHS Blood and Transplant website and the Anthony Nolan website have more information about stem cell and bone marrow donation.

Page last reviewed: 09/08/2018Next review due: 09/08/2021

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Stem cell and bone marrow transplants - NHS

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To prepare your body for bone marrow or stem cell transplant, youll be treated with high doses of chemotherapy with or without radiation to destroy cancerous cells. Some healthy cells may also be destroyed, which can cause unpleasant side effects. These side effects typically go away after a few weeks.

Once this preparation is complete, new stem cells will be transplanted through your veins and the cells will make their way to your bone marrow. These stem cells will mature into healthy marrow, to produces healthy blood and immune cells.

Stem cells transplants can come from your own bone marrow (autologous) or a donors marrow (allogeneic). Whether autologous or allogeneic stem cells are used depends on your condition, and the procedures have some differences.

Uses your own stem cells. Before chemotherapy, your stem cells are collected by apheresis, frozen with a preservative and stored until they are needed. Because the cells are yours, theres no risk of your body rejecting the transplanted stem cells. This method is appropriate for blood-related cancers like multiple myeloma, non-Hodgkin lymphomas and Hodgkin disease, as well as certain germ-cell cancers.

Use healthy cells from a donor, when an immunological effect is needed to fight your cancer. Your donor will usually be a sibling or a strong match from the national registry. If a matched sibling or unrelated donor cannot be found, cord blood stem cells or a mismatched relative donor may be used.

The donors stem cells are collected by apheresis or from the bone marrow in a surgical procedure. Youll need to take medicines to suppress your immune system to prevent rejection and keep the donors immune cells from attacking your normal cells. Donor-cell transplant is used to treat blood-related cancers like leukemias and some lymphomas or multiple myeloma, and bone marrow failure disorders like myelodysplastic syndrome and aplastic anemia.

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Bone Marrow & Stem Cell Transplant | IU Health

Bone Marrow Stem Cells Comments Off on Bone Marrow & Stem Cell Transplant | IU Health | November 28th, 2018

The science behind skin care has been progressing at a faster and faster rate of speed. Twenty years ago, had you mentioned stem cell use in association with mainstream skin care, people would have stared at you as though you had three heads and steered their children in a path far around you.

Reality today paints a much cooler picture. One where stem cells are used to treat a variety of blood and bone marrow diseases, blood cancers, and immune disorders. And we are finding stem cells, both human and plant, on the ingredients lists of some very powerful and effective skin care products. Stem cell use in skin care products is coming of age.

Stem cells are a type of cell that are found in all living things and have the glorious ability to differentiate themselves into many different types of cells. They are capable of becoming any other type of cell in that type of organism and reproducing in a controlled manner. As a result, they are the building blocks of your tissues and have the unique ability to replace damaged and diseased cells. They can proliferate for long periods, dividing themselves over and over again into millions of new cells. That means they can play a pivotal role in how skin repairs itself.

Stem cells are extremely beneficial in the natural process of healing and regeneration, says Jessica Weiser, M.D., a board-certified dermatologist in New York City.

Many beauty products contain stem cells from fruits like Swiss apples, edelweiss, roses, date palms, grape, raspberry, lilac, and gotu kola that have the ability to stay fresh for long periods of times.

Human stem cells come from one of two sources: embryonic stem cells and adult (somatic) stem cells. For the case of skin care, stem cells of the adult origin are used. They remain in the body quietly in a non-dividing state for years until activated by disease or injury.

Because they play an essential role in tissue removal, stem cells residing just below the surface of the skin can help with restorative functions, such as cellular regeneration, and could play a vital role in helping to enhance our ability to repair aging skin.

You start off with an abundance of stem cells in your skin, but you lose them as you age. By the time you hit 50, youve lost about 98% of them.

The working theory is that by applying products containing stem cell extracts, you could encourage the growth of your own skins stem cells and possibly wake them up to trigger their anti-aging effects. Some research suggests that they can promote the production of collagen, which is the bodys firming protein.

Live cells need very specific conditions to remain alive and viable. Its difficult enough to maintain those conditions in a laboratory setting. Skin care products and their environments dont offer those types of conditions. When stem cells are included in skin care products, makers arent looking to provide you with live, functional cells. Extracts from the stem cells, not the actual cells themselves, are usually added to skin care products. Its not possible to maintain live stem cells in cosmetic emulsions, says Zoe Diana Draelos, a consulting professor of dermatology at the Duke University School of Medicine in Durham, North Carolina.

Most stem cell products you see on the shelf dont actually contain stem cells, but rather the proteins and amino acids that those cells secrete. Typically, if you see a product labeled as a stem cell product, youll see the stem cells key substances in the ingredients list. These include ferulic acid, ellagic acid, and quercetin. This is what your body is able to recognize and put to use to help rejuvenate and repair cells. Human stem cell byproducts (from skin or adipose tissue) seem to be the best solution for use in skin care products because of their ability to produce the same types of cellular components that your body uses naturally to maintain a youthful appearance.

Cultivating stem cells is a tedious process involving a very controlled environment without any contaminants in order to yield the most potent, stable, and pure extract. Because of this technology, the cost of stem cell products are usually greater than products without.

MDSUN is a perfect collaboration between medicine and beauty with the ability to deliver the highest quality skin care products, giving you long-lasting radiance and youth. Each formulation is effective, while free of harsh ingredients, perfumes, or chemical scent additives.

They offer multiple options incorporating powerful stem cell technology with proven effective results. The Wrinkle Smoothener reduces wrinkle depth and improves skins texture while quenching skin-damaging free radicals. It can stimulate skin repair and diminish the appearance of aging skin.

The Collagen Lift is a very potent treatment that can deliver obvious results, minimizing the appearance of wrinkles and lines, improving skin texture and tone. This luxurious gel-cream soothes redness and irritations and rejuvenates skin cells for a strong and long-lasting radiant renewal.

The Med-Eye Complex Cream visibly promotes firmness, increases blood circulation and deeply hydrates the eye area to reduce the signs of aging, lending a youthful appearance and glow.

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Stem Cell Use in Skin Care Products? - Science of Skincare

Skin Stem Cells Comments Off on Stem Cell Use in Skin Care Products? – Science of Skincare | November 24th, 2018

Human life is dependent upon the hearts ability to pump forcefully and frequently enough, but heart failure signs can disturb its normal function. Most humans cannot live more than four minutes without a heartbeat or continuous blood-flow. At that time, brain cells begin to die because they lack adequately oxygenated blood-flow.

The human adult body requires, on average, 5.0 liters of re-circulated blood per minute. In the cardiology field, this metric is called the Cardiac Output, which is calculated as Stroke Volume (SV) x Heart Rate (HR). Another key metric is a patients Ejection-Fraction (EF %). A patients EF tells a cardiologist and other physicians if his or her heart is functioning normally or low normally. It is a measurement of ones heart contraction, with a normal EF range being 55-70%.

This number can also be combined with a patients heart rate to provide physicians with a baseline of a patients cardiac status. A normal range for an adult is 60-100 beats per minute, and this can be significantly higher during a normal pregnancy.

In this article:

For a cardiologist, cardiac metrics indicate if their services are required and allowthem to sign-off on pre-operative cardiac clearances. For other physicians, it tells them if the organ which they specialize in is being perfused adequately (for example, a nephrologist would be interested to know kidney perfusion). It can also indicate the degree to which decreased heart function may affect the severity or spread of disease.

When the heart fails to contract forcefully enough and its performance decreases to the point where its ability to circulate blood adequately is compromised (the EF% falls below 40%), this is considered heart failure. The clinical parameters of heart failure are clearly defined by the New York Heart Association (NYHA), which places patients in NYHA Class III & IV into the heart failure category.

An echocardiogram (often called an Echo), as opposed to an Electrocardiogram (EKG or ECG), allows technicians and physicians to visualize the beating heart. Video clips of the heart contracting are digitally recorded, and a patients EF and Cardiac Output (CO) can be measured with several diagnostic tools (Fractional Shortening via 2D or M-Mode measurements and Simpsons Method via 2D and 3D Quantification) on a cardiovascular ultrasound system.

When an experienced echo tech or cardiologist views a failing heart, it is immediately apparent. Based on my experience reading echocardiograms, I can see that the heart walls or heart muscles (myocardium) are not contracting as vigorously as they should.

For patients with a 5% EF range, any physical movement is extremely strenuous, and they can go into cardiac arrest at any moment, which is why they are usually on cardiac telemetry in a hospital setting. Most likely, a patient with 5% EF range would be awaiting a heart transplant, unless there is a medical condition preventing them from being eligible.

Once a patient falls into the heart failure range, they will be lethargic and have severe limits on activities. Other clinical manifestations of heart failure can include peripheral edema (i.e. swelling in the feet, legs, ankles, or stomach), pulmonary edema, and shortness of breath. In many cases, this can lead to depression.

In evaluating the frequency of heart failure in the U.S, statistics from the U.S. Centers for Disease Control (CDC) find that approximately 5.7 million adults are afflicted with this condition. Additionally, care for congestive heart failure costs an estimated $30.7B per year. Furthermore, the mortality rates of patients suffering from heart failure indicate its clinical severity, with 1 in 5 patients with this condition dying within a year of receiving the diagnosis.

A patient experiencing severe heart failure has limited treatment options, which are expensive, complicated, and have major lifestyle implications.

These limited options include:

Consequently, physicians need more effective weapons for treating heart failure in order to improve patients lives and reduce healthcare-related costs. CHF patients have disproportionate hospital readmission rates when compared to other major diseases.

Enter in the growing field of cardiac stem cell treatments, which introduce fundamentally new treatment options for heart failure patients. In cardiac stem cell treatments, stem cells are taken from a patients bone marrow or fat tissue in a sterile surgical procedure and injected via a catheter-wire into infarcted or poorly contracting muscular segments of the hearts main pumping chamber, the left ventricle (LV).

Over the course of a few months, the stem cells impact myocardial cells and begin to improve the contractility of the affected segments, most likely through paracrine signaling mechanisms and impacting the local microenvironment. This can bring a patients EF to low-normal or even normal levels. As a result, a patient can live a more normal life and return to many activities.

A very early clinical trial aimed at evaluating the potential and effectiveness of cardiac stem cell therapy in humans was conducted in 2006 utilizing a commercial product, VesCellTM. The parameters and results of this trial were documented in the American Heart Associations Circulation, Abstract 3682: Treatment of Patients with Severe Angina Pectoris Using Intracoronarily Injected Autologous Blood-Borne Angiogenic Cell Precursors.The subjects of this trial received an intracoronary injection of VesCellTM, an Autologous Angiogenic Cell Precursor (ACP)-based product.

The authors drew their conclusion regarding this study. VesCell therapy for chronic stable angina seems to be safe and improves anginal symptoms at 3 and 6 months. Larger studies are being initiated to evaluate the benefit of VesCell for the treatment of this and additional severe heart diseases. (Source: Tresukosol et al. Abstract 3682: Treatment of Patients with Severe Angina Pectoris Using Intracoronarily Injected Autologous Blood-Borne Angiogenic Cell Precursors. Circulation. October 31, 2006. Vol. 114, Issue Suppl 18. Link: http://circ.ahajournals.org/content/114/Suppl_18/II_786.4 )

Another early cardiac stem cell clinical trial was performed in 2009 by a Cedars-Sinai team based on technologies and discoveries made by Eduardo Marban, MD, PhD, and led by Raj Makkar, MD. In this study, they explored the safety of harvesting, expanding, and administering a patients cardiac stem cells to repair heart tissue injured by myocardial infarction.

Recently, the American College of Cardiology (ACC) also announced results of a ground-breaking clinical study to evaluate the efficacy and effectiveness of cardiac stem cell treatment for heart failure patients. As stated by Timothy Henry, M.D., Director of Cardiology at Cedars-Sinai Heart Institute and one of the studys lead authors, This is the largest double-blind, placebo-controlled stem cell trial for treatment of heart failure to be presentedBased on these positive results, we are encouraged that this is an attractive potential therapy for patients with class III and class IV heart failure.

Additionally, Dr. Charles Goldthwaite, Jr, published a whitepaper titled, Mending a Broken Heart: Stem Cells and Cardiac Repair, in which he draws the conclusion, Given the worldwide prevalence of cardiac dysfunction and the limited availability of tissue for cardiac transplantation, stem cells could ultimately fulfill a large-scale unmet clinical need and improve the quality of life for millions of people with CVD. However, the use of these cells in this setting is currently in its infancymuch remains to be learned about the mechanisms by which stem cells repair and regenerate myocardium, the optimal cell types, and modes of their delivery, and the safety issues that will accompany their use.

Clearly, there is a trend toward acceptance of cardiac stem cell therapies as an emerging treatment option. Several world-renowned institutes are now conducting clinical studies involving cardiac stem cell treatment, as well as applying for intellectual property protection (patents) pertaining to the techniques required in administrating the therapies.

The key questions at this point in time appear to be:

An important whitepaper pertaining to cardiac stem cells is Ischemic Cardiomyopathy Patients Treated with Autologous Angiogenic and Cardio-Regenerative Progenitor Cells, written by Dr. Athina Kyritsis, et al. In it, the physicians describe their objective as investigating the feasibility, safety, and clinical outcome of patients with Ischemic Cardiomyopathy treated with Autologous Angiogenic and Cardio-Regenerative Progenitor cells (ACPs).

The researchers state: In numerous human trials there is evidence of improvement in the ejection fractions of Cardiomyopathy patients treated with ACPs. Animal experiments not only show improvement in cardiac function, but also engraftment and differentiation of ACPs into cardiomyocytes, as well as neo-vascularization in infarcted myocardium. In our clinical experience, the process has shown to be safe as well as effective.

The authors also found that patients treated with this approach gained increases in cardiac ejection fraction from their starting measurements, with improvements in their cardiac ejection fraction of 21 points (75% increase) at rest and 28.5 points (80% increase) at stress. As a result of these finding, the authors conclude, ACPs can improve the ejection fraction in patients with severely reduced cardiac function with benefits sustained to six months.

In the practice of medicine, the focus should be on delivering excellent care to patients. If there are cardiac stem cell treatments available, then regulatory obstacles should be removed when sufficient clinical trial evidence has been provided to indicate safety and efficacy.

Cardiologist Zannos Grekos, MD, a pioneer in cardiac stem cell therapy since 2006, points to the vastly untapped promise of related therapies, commenting Those of us that have been involved with cardiac stem cell treatment for the last 10-plus years can see the incredible potential this approach has.

As of 2017, the U.S. healthcare system is under enormous pressure to deliver affordable healthcareto a growing population of patients, especially those who are fully or partially covered under Medicare or Medicaid (many have secondary coverage). Although we are in the infancy of its development, cardiac stem cell treatments represent a potentially powerful treatment alternative to patients with heart failure symptoms.

To learn more, view the resources below.

1) Regenocyte http://www.regenocyte.com

2) Cleveland Clinic Stem Cell Therapy for Heart Disease my.clevelandclinic.org/health/articles/stem-cell-therapy-heart-disease

3) Harvard Stem Cell Institute (HSCI) hsci.harvard.edu/heart-disease-0

4) Cedars Sinai Cardiac Stem Cell Treatment http://www.cedars-sinai.edu/Patients/Programs-and-Services/Heart-Institute/Clinical-Trials/Cardiac-Stem-Cell-Research.aspx

5) Johns Hopkins Medicine Cardiac Stem Cell Treatments http://www.hopkinsmedicine.org/stem_cell_research/cell_therapy/a_new_path_for_cardiac_stem_cells.html

What do you think about heart failure signs and cardiac stem cell therapies? Share your thoughts in the comments section below.

Up Next:European Society of Cardiology (ESC) Congress Presentation Reveals Results From Pre-Clinical Study Using CardioCells Stem Cells for Acute Myocardial Infarction

Guest Post: This is a guest article by Clifford M. Thornton, a Certified Cardiovascular Technologist, experienced Echocardiographer Technician, and journalist in the cardiac and medical device fields. His articles have been published in Inventors Digest, Global Innovation Magazine, and Modern Health Talk. He is enthusiastic about progress with cardiac stem cell therapies and their role in heart failure treatment.He can be reached byphone at 267-524-7144 or by email at[emailprotected].

Editors Note This post was originally published on March 14, 2017, and has been updated for quality and relevancy.

Heart Failure Signs | Cardiac Stem Cell Therapies for Heart Failure Treatment

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Cardiac Stem Cells Comments Off on Heart Failure Signs | Cardiac Stem Cell Therapies: Heart … | November 15th, 2018

SC21 BioTech: Stem Cell Skin Care Set

SC21 nowoffers a rejuvenating stem cell skin careset that is available to help restore aging skin. At SC21, we have been able to combine human mesenchymal stem cell growth factors, polypeptide complexes, and cytokines, with our day time anti-aging cream & evening hydration serum.

Our SC21 biotechnology scientists have developed a process to isolate potent rejuvenating factors from human stem cells. By resupplying the skin with these powerful missing factors, SC21 Day & Night Stem Cell Skin Care promotes cell renewal, boosts the production of collagen and elastin, restores aging cells, and, ultimately, provides you with more youthful looking skin.

It is important to note that as we age, the stem cell population that is vital in providing healing signals to the skin dramatically diminishes. As a result of this, the rejuvenating components the skin needs to maintain its appearance lessen. By replenishing lost peptides, cytokines & growth factors with the use of a topical product on the skin, we, through the day &night skin care set, are able to effectively re-engage the skins healing process.

The SC21 day & night stem cell skin care rejuvenation set also has a complete solution for restoring aging skin. We have, through the day anti-aging cream & night hydration serum been able to use: human mesenchymal stem cell growth factors, to regenerate human tissues; polypeptide complexes, (which penetrate the epidermis, outer layer of our skin) to send signals to the skin cells and cytokines proteins to send signals between the skin cells.

Focus Ingredient of Growth Factor Skin Care:

Mesenchymal Stem Cell (MSC) Peptide Complex = 15% (cytokines, growth factors, peptide complex)

Other Key Ingredients:

Focus Ingredient of Growth Factor Skin Care:

Mesenchymal Stem Cell (MSC) Peptide Complex = 20%(cytokines, growth factors, peptide complex)

Other Key Ingredients:

Apply 2-3 pumps to clean & dry skin.

Peptides are easier explained as signaling molecules produced by cells to instruct other cells.

As cellular messengers, cytokines influence and control our biological processes from start to finish. There are hundreds of unique cytokines in the human body. Cells talk with cytokines to repair injury, repel microbes, fight infections, and develop immunity.

Growth factors, are, on the other hand, diffusible signaling proteins that stimulate the growth of specific tissues and play a crucial role in promoting cell differentiation and division.

Many modern medical advances, including stem cell breakthroughs, are made possible due to our growing understanding of cytokines & growth factors. We use modern culture techniques (the same type used to produce human insulin and other naturally occurring substances) to grow human stem cells in the laboratory to harvest their regenerative cytokines and growth factors.

Mesenchymal stem cells (MSCs), which are traditionally found in the bone marrow, are used to improve function upon integration because they are self-renewing cells that have the capacity to differentiate, and are capable of replacing and repairing damaged tissues.

MSCs can consequently during culture, produce the following:

Our skin cells are biologically designed to continuously renew themselves, but, starting from our mid 20s, the skin cell renewal process slows down and our skin becomes thinner. This thinning causes us to be more prone to skin damage from external elements.

However, there are other factors that can contribute to our aging process, and in other cases even cause premature aging. Some of these factors include:

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Stem Cell Skin Care - anti-aging cream and hydration Serum

Skin Stem Cells Comments Off on Stem Cell Skin Care – anti-aging cream and hydration Serum | November 14th, 2018

Marc Darrow MD, JD. Thank you for reading my article. You can ask me your questions aboutthis articleusing the contact form below.

I want to begin this article with a case study from our recently published research in theBiomedical Journal of Scientific & Technical Research.

Afterphysical assessment of her lower back, we determinedher pain was generated from a lumbosacral sprain. Not the narrowing of the L1-L5,S1

She had oneBone marrow derived stem cell treatment and at first follow up two weeks after the injections,the patient experienced no pain or stiffness and reported 90% total improvement. Approximately a year after treatment, she felt evenbetter, and stated that she was able to perform aerobics and line dancing for an hour and a half a day with no pain. She reportedinfrequent stiffness, but not as severe as it was prior to treatment.

Her resting and active pain were 0/10 and functionality score was 39/40.(1)

This was one document case in the medical literature. Over the years we have helped many people avoid a stenosis surgery they did not want or possibly did not even need.

Despite the fact that many studies insist that surgical treatment is the best option for lumbar spinal stenosis, a startling study was published in the medical journal Spine. In this study, American, Canadian and Italian researchers published their evidence:

We have very little confidence to conclude whether surgicaltreatmentor a conservative approach is better forlumbarspinal stenosis, and we can provide no new recommendations to guide clinical practice. . .However, it should be noted that the rate of side effects ranged from 10% to 24% in surgical cases, and no side effects were reported for any conservativetreatment. (2)

In the above research it should be pointed out the comparison between lumbar surgery and conservative treatments did not include stem cell therapy. They included the traditional conservative treatments including physical therapy, cortisone injections, pain medications and others listed below.

One of the reasons surgery may be no better than conservative care is that the surgery tried to fix a problem that was not there: Pain.

In the medical journal Osteoarthritis and Cartilage,doctors reported that many asymptomatic individuals, those with no pain or other challenges, have radiographic lumbar spinal stenosis. In other words they only have lumbar spinal stenosis on the MRI.

The doctors noted:

A diagnosis of spinal stenosis can be frightening because of the implications that a surgery may be needed to avoid paralysis.It is important to note that in instances where stenosis is so severe that the patient has lost circulation to the legs or bladder control a surgical consult should be made immediately.

In the December 2017 edition of the medical journal Spine, doctors from the University of Pittsburgh and University Toronto reported these observations in patients seeking non-surgical treatments for lumbar spinal stenosis.

Individuals with lumbar spinal stenosis may believe misinformation and information from non-medical sources, especially when medical providers do not spend sufficient time explaining the disease process and the reasoning behind treatment strategies. Receiving individualized care focused on self-management led to fewer negative emotions toward care and the disease process. Clinicians should be prepared to address all three of these aspects when providing care to individuals with lumbar spinal stenosis.(4)

Back pain can certainly cause anxiety, depression, and catastrophizing thoughts. The people in this study wanted education and involvement in their choice of treatment. I hope I can provide some for you here in this article.

Lumbar Spinal Stenosis is a narrowing of the space between vertebrae where the spinal cord and the spinal nerves travel. It is a diagnostic term to describe lower back pain with or without weakness and loss of sensation in the legs. It is a very common condition brought on mostly by aging and the accompanying degeneration of the spine.

In the recommended surgical procedures for spinal stenosis, two choices are the most favored.

A paper published in October 2017 gives a good outline where conservative medicine is in the treatment of Lumbar stenosis. It is from doctors at the University of South Carolina

This is indeed a fair assessment of SOME of the treatment options available to patients.However, not all doctors agree. At New York University in June 2017 research, doctors wrote:

The highest levels of evidence do not support minimally invasive surgery over open surgery for cervical orlumbardisc herniation. However, minimally invasive surgery fusion demonstrates advantages along with higher revision and hospital readmission rates. These results should optimize informed decision-making regarding minimally invasive surgery versus open spine surgery, particularly in the current advertising climate greatly favoring minimally invasive surgery.(6)

Researchers at theUniversity of Sydneysay that the evidence for recommending lumbar spinal surgery as the best option to patients is lacking and it is possible that a sham or placebo surgery can deliver the same results.(7)

In the research I cited at the top of this article, doctors at the Italian Scientific Spine Institute in Milanwrote: We cannot conclude on the basis of this review whether surgical or nonsurgical treatment is better for individuals with lumbar spinal stenosis. We can however report on the high rate of effects reported in three of five surgical groups and that no side effects were reported for any of the conservative treatment options.(8)

Considering the majority of these procedures are unnecessarily being performed for degenerative disc disease alone, spine surgeons should be increasingly asked why they are offering these operations to their patients

Ateam of Japanese researchers found thatpatients with lumbar spinal stenosiswho do not improve after nonsurgical treatments are typically treated surgically using decompressive surgeryand spinal fusion surgery. Unfortunately the researchers could not determine if the surgery had any benefit either.(9)Maybe the patients problem was not the stenosis?

Now lets go to another paper that has more of an opinion: From Dr. Nancy Epstein ofWinthrop University Hospital:

Surgeons at Leiden University Medical Centre in the Netherlandsspeculate that doctors go into a diagnosis oflumbar spinal stenosis with the thought that there is osteoarthritis a bony overgrowth on the spinal nerves. Once determined, the symptoms of patients can be categorized into two groups; regional (low back pain, stiffness, and so on) or radicular (spinal stenosis mainly presenting as neurogenic claudication nerve inflammation).

In the patients who primarily complain of radiculopathy (radiating leg pain) with an stable spine, a decompression surgery may be recommendedto removebonefrom around thenerve root to give the nerve root more space.The surgeons warn of thefear that surgery to a stable spine will make it unstable.(11)

Afusion procedure to limit the movement between two vertebrae and hopefully stop the compression of nerves is another option. As mentioned by independent research above surgery for spinal stenosis should onlybe considered after conservative therapies have been exhausted.Surgical treatment of lumbar spinal disorders, including fusion, is associated with a substantial risk of intraoperative and perioperative complications,as pointed out in the research by surgeons from Catholic University in Rome.(12)

Bone growth occurs in the spine because the bone is trying to stabilize the spine from excessive movement or laxity. Fusion surgery is recommended as a means to accelerate that type of stabilization. Regenerative medicine includingPRP andStem Cell Therapy(watch the video)works in a completely different way. Theystabilize the spine by strengthening the often forgotten and underappreciated spinal ligaments and tendons.These techniques help stabilize the spine, which is imperative as unstable joints can lead to or further exacerbate the arthritis that causes spinal stenosis.

In the medical journal Insights into imaging, researchers wrote of the four factors associated with the degenerative changes of the spine that cause spinal canal stenosis:

The same research suggests that these conditions can prevent the formation of new tissue (collagen) which can initiate repair.(13)

Collagen is of course the elastic material of skin and ligaments. Here the association between collagen interruption and spinal stenosis can be made to show spinal instability can be THE problem of symptomatic stenosis.

A fascinating study on what damaged spinal ligaments can do

A fascinating study in the Asian Spine Journal investigated the relationship between ligamentum flavum thickening and lumbar segmental instability, disc degeneration, and facet joint osteoarthritis. Ligament thickening is the result of chronic inflammation. Chronic ligament inflammation is the result of a ligament injury that is not healing.

What these researchers found was a significant correlation between ligamentum flavum thickness, spinal instability and disc degeneration. More so, the worse the degenerative disc disease, the worse the ligamentum flavum thickness.(14)

PRP and stem cells address the problem of ligament damage and inflammation. Addressing these problems address the problems of spinal instability. Addressing the problems of spinal instability can address the problems of spinal and cervical stenosis.

A leading provider of bone marrow derived stem cell therapy, Platelet Rich Plasma and Prolotherapy11645 WILSHIRE BOULEVARD SUITE 120, LOS ANGELES, CA 90025

PHONE: (800) 300-9300

1 Darrow M, Shaw BS. Treatment of Lower Back Pain with Bone Marrow Concentrate. Biomed J Sci&Tech Res 7(2)-2018. BJSTR. MS.ID.001461. DOI: 10.26717/ BJSTR.2018.07.001461.

2 Zaina F, TomkinsLane C, Carragee E, Negrini S. Surgical versus nonsurgical treatment for lumbar spinal stenosis. The Cochrane Library. 2016 Jul 1.

3 Lynch AD, Bove AM, Ammendolia C, Schneider M. Individuals with lumbar spinal stenosis seek education and care focused on self-managementresults of focus groups among participants enrolled in a randomized controlled trial. The Spine Journal. 2017 Dec 12

4 Ishimoto Y, Yoshimura N, Muraki S, Yamada H, Nagata K, Hashizume H, Takiguchi N, Minamide A, Oka H, Kawaguchi H, Nakamura K. Associations between radiographic lumbar spinal stenosis and clinical symptoms in the general population: the Wakayama Spine Study. Osteoarthritis and cartilage. 2013 Jun 1;21(6):783-8.

5Patel J, Osburn I, Wanaselja A, Nobles R. Optimal treatment for lumbar spinal stenosis: an update. Current Opinion in Anesthesiology. 2017 Oct 1;30(5):598-603.

6 Vazan M, Gempt J, Meyer B, Buchmann N, Ryang YM. Minimally invasive transforaminal lumbar interbody fusion versus open transforaminal lumbar interbody fusion: a technical description and review of the literature. Acta Neurochir (Wien). 2017 Jun;159(6):1137-1146

7Machado GC, Ferreira PH, Yoo RI, et al. Surgical options for lumbar spinal stenosis. Cochrane Database Syst Rev. 2016 Nov 1;11:CD012421.

8Zaina F, Tomkins-Lane C, Carragee E, Negrini S. Surgical Versus Nonsurgical Treatment for Lumbar Spinal Stenosis. Spine (Phila Pa 1976). 2016 Jul 15;41(14):E857-68.

9 Inoue G, Miyagi M, Takaso M. Surgical and nonsurgical treatments for lumbar spinal stenosis. Eur J Orthop Surg Traumatol. 2016 Oct;26(7):695-704. doi: 10.1007/s00590-016-1818-3. Epub 2016 Jul 25.

10 Epstein NE. More nerve root injuries occur with minimally invasive lumbar surgery: Lets tell someone. Surg Neurol Int. 2016 Jan 25;7(Suppl 3):S96-S101. doi: 10.4103/2152-7806.174896. eCollection 2016.

11Overdevest GM, Moojen WA, Arts MP, Vleggeert-Lankamp CL, Jacobs WC, Peul WC.Management of lumbar spinal stenosis: a survey among Dutch spine surgeons. Acta Neurochir (Wien). 2014 Aug 7. [Epub ahead of print]

12.Proietti L, Scaramuzzo L, Schiro GR, Sessa S, Logroscino CA. Complications in lumbar spine surgery: A retrospective analysis. Indian J Orthop. 2013 Jul;47(4):340-5. doi: 10.4103/0019-5413.114909.

13 Kushchayev SV, Glushko T, Jarraya M, et al. ABCs of the degenerative spine.Insights into Imaging. 2018;9(2):253-274. doi:10.1007/s13244-017-0584-z.

14 Yoshiiwa T, Miyazaki M, Notani N, Ishihara T, Kawano M, Tsumura H. Analysis of the Relationship between Ligamentum Flavum Thickening and Lumbar Segmental Instability, Disc Degeneration, and Facet Joint Osteoarthritis in Lumbar Spinal Stenosis.Asian Spine Journal. 2016;10(6):1132-1140. doi:10.4184/asj.2016.10.6.1132.2373

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Stem cells for stenosis - Dr. Marc Darrow is a Stem Cell ...

Spinal Cord Stem Cells Comments Off on Stem cells for stenosis – Dr. Marc Darrow is a Stem Cell … | October 14th, 2018

With patches of stem cells on their broken spinal cords, partially paralyzed rats once againreached out and grabbed distant treats, researchers report in Nature Medicine.

While previous studies have shown progress in regenerating certain types of nerve cells in injured spinal cords, the study is the first to coax the regrowth of a specific set of nerve cells, called corticospinal axons. These bundles of biological wiring carry signals from the brain to the spinal cord and are critical for voluntary movement. In the study, researchers were able to use stem cells from rats and humans to mend the injured rodents.

The corticospinal projection is the most important motor system in humans, senior author Mark Tuszynski at the University of California, San Diego said. It has not been successfully regenerated before. Many have tried, many have failedincluding us, in previous efforts.

For the study, the researchers used rat and human neural progenitor cells, which can produce several different types of cells found in the central nervous system. The researchers coaxed the cells into forming spinal cord tissue using specific chemical signals. When injected into the damaged spinal cords of rats, the cells took root, filling lesions with new tissue and corticospinal axons. And the new nerve cells linked up with the severed connections left hanging from the injury, allowing signals to traverse the patch.

In mobility tests, injured rats that got the spinal patch could better stretch out their front legs to grab hard-to-reach treats compared with injured rats without the stem-cell grafts.

Still, the cord-patching method is far from clinical use in humans, the authors caution. Researchers will need to follow the rats to look at long-term safety and effectiveness of the patches. Then, they'll have to try out the patches in other animal models before optimizing the method for humans.

But,Tuszynski said, "now that we can regenerate the most important motor system for humans, I think that the potential for translation is more promising."

Nature Medicine, 2015. DOI: 10.1038/nm.4066 (About DOIs).

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Scientists regenerate spinal cord in injured rats with ...

Spinal Cord Stem Cells Comments Off on Scientists regenerate spinal cord in injured rats with … | September 28th, 2018

Are there enough stem cells in your knees to heal the damage of osteoarthritis? If yes, why arent those stem cells fixing your knees now? Is it a lack of numbers?

Marc Darrow MD, JD. Thank you for reading my article. You can ask me your questions about bone marrow derived stem cells using the contact form below.

In 2011, doctors at the University of Aberdeen published research in the journal Arthritis and rheumatism that provided the first evidence that resident stem cells in the knee joint synovium underwent proliferation (multiplied) and chondrogenic differentiation (made themselves into cartilage cells) following injury.(1)

If the stem cells in your knee synovial lining are abundant and have the ability to rebuild cartilage after injury, why isnt your knee fixing itself?

One of those 40 studies was performed by researchers at theUniversity of Calgary in 2012. Among their questions, if the stem cells in the knee synovial lining are abundant and have the ability to rebuild cartilage after injury, why isnt the knee fixing itself? Here is what they published:

Since osteoarthritis leads to a progressive loss of cartilage and synovial progenitors (rebuilding) cells have the potential to contribute to articular cartilage repair, the inability of osteoarthritis synovial fluid Mesenchymal progenitor cells (stem cell growth factors) to spontaneously differentiate into chondrocytes suggests that cell-to-cell aggregation and/or communication may be impaired in osteoarthritis and somehow dampen the normal mechanism of chondrocyte replenishment from the synovium or synovial fluid. Should the cells of the synovium or synovial fluid be a reservoir of stem cells for normal articular cartilage maintenance and repair, these endogenous sources of chondro-biased cells would be a fundamental and new strategy for treating osteoarthritis and cartilage injury if this loss of aggregation & differentiation phenotype can be overcome.(2)

This research was supported in anew study from December 2017 In Nature reviews. The paper suggested that recognizing that joint-resident stem cells are comparatively abundant in the joint and occupy multiple niches (from the center of the joint to the out edges) will enable the optimization of single-stage therapeutic interventions for osteoarthritis.(3) The idea is to get these native stem cells to repair.

Now we know that there are many stem cells in the knee, when there is an injury there are more stem cells. If we can figure out how to get these stem cells turned on to the healing mode, the knee could heal itself of early stage osteoarthritis. So the problem is not the number of stem cells, BUT, communication.

This failure to communicate was also seen in other research. In 2016, another heavily cited paper, this time fromTehran University for Medical Sciences, noted that despite their larger numbers,the native stem cells act chaotically and are unable to regroup themselves into a healing mechanism and repair the bone, cartilage and other tissue. Introducing bone marrow stem cells into this environmentgets the native stem cells in line and redirects them to perform healing functions. The joint environmentis changed from chaotic to healing because of communication.(4) It should be pointed out that at the time of this article update (August 2018) 62 medical studies cited the research in this papers findings).

A recentpaper from a research team inAustralia confirms how this change of joint environment works. It starts with cell signalling a new communication network is built.

University of Iowa research published in theJournal of orthopaedic research

Serious meniscus injuries seldom heal and increase the risk for knee osteoarthritis; thus, there is a need to develop new reparative therapies. In that regard, stimulating tissue regeneration by autologous (from you, not donated) stem/progenitor cells has emerged as a promising new strategy.

(The research team) showed previously that migratory chondrogenic progenitor cells (mobile cartilage growth factors) were recruited to injured cartilage, where they showed a capability in situ (on the spot) tissue repair. Here, we tested the hypothesis that the meniscus contains a similar population of regenerative cells.

Explant studies revealed that migrating cells were mainly confined to the red zone (where the blood is and its growth factors) in normal menisci: However, these cells were capable of repopulating defects made in the white zone (the desert area where no blood flows. Migrating cell numbers increased dramatically in damaged meniscus. Relative to non-migrating meniscus cells, migrating cells were more clonogenic, overexpressed progenitor cell markers, and included a larger side population. (They were ready to heal) Gene expression profiling showed that the migrating population was more similar tochondrogenic progenitor cells (mobile cartilage growth factors) than other meniscus cells. Finally, migrating cells equaledchondrogenic progenitor cells in chondrogenic potential, indicating a capacity for repair of the cartilaginous white zone of the meniscus. These findings demonstrate that, much as in articular cartilage, injuries to the meniscus mobilize an intrinsic progenitor cell population with strong reparative potential.(6)

The intrinsic progenitor cell population with strong reparative potential are in your knee waiting to be mobilized.

So what are we to make of this research?There are a lot of stem cells in a knee waiting to repair. The problem is they are confused and not getting the correct instructions. Bone marrow stem cell therapy can fix the communication problem and begin the repair process anew.

A leading provider of bone marrow derived stem cell therapy, Platelet Rich Plasma and Prolotherapy11645 WILSHIRE BOULEVARD SUITE 120, LOS ANGELES, CA 90025

PHONE: (800) 300-9300

1 Kurth TB, Dellaccio F, Crouch V, Augello A, Sharpe PT, De Bari C. Functional mesenchymal stem cell niches in adult mouse knee joint synovium in vivo. Arthritis Rheum. 2011 May;63(5):1289-300. doi: 10.1002/art.30234.

2 Krawetz RJ, Wu YE, Martin L, Rattner JB, Matyas JR, Hart DA. Synovial Fluid Progenitors Expressing CD90+ from Normal but Not Osteoarthritic Joints Undergo Chondrogenic Differentiation without Micro-Mass Culture. Kerkis I, ed.PLoS ONE. 2012;7(8):e43616. doi:10.1371/journal.pone.0043616.

3 McGonagle D, Baboolal TG, Jones E. Native joint-resident mesenchymal stem cells for cartilage repair in osteoarthritis. Nature Reviews Rheumatology. 2017 Dec;13(12):719.

4Davatchi F, et al. Mesenchymal stem cell therapy for knee osteoarthritis: 5 years follow-up of three patients. Int J Rheum Dis. 2016 Mar;19(3):219-25.

5. Freitag J, Bates D, Boyd R, Shah K, Barnard A, Huguenin L, Tenen A.Mesenchymal stem cell therapy in the treatment of osteoarthritis: reparative pathways, safety and efficacy a review.BMC Musculoskelet Disord. 2016 May 26;17(1):230. doi: 10.1186/s12891-016-1085-9. Review.

6 Seol D, Zhou C, et al. Characteristics of meniscus progenitor cells migrated from injured meniscus. J Orthop Res. 2016 Nov 3. doi: 10.1002/jor.23472.

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Are there enough stem cells in your knees to heal the ...

Skin Stem Cells Comments Off on Are there enough stem cells in your knees to heal the … | September 24th, 2018

Embryonic stem cells (ES cells or ESCs) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre-implantation embryo.[1][2] Human embryos reach the blastocyst stage 45 days post fertilization, at which time they consist of 50150 cells. Isolating the embryoblast, or inner cell mass (ICM) results in destruction of the blastocyst, a process which raises ethical issues, including whether or not embryos at the pre-implantation stage should have the same moral considerations as embryos in the post-implantation stage of development.[3][4] Researchers are currently focusing heavily on the therapeutic potential of embryonic stem cells, with clinical use being the goal for many labs. These cells are being studied to be used as clinical therapies, models of genetic disorders, and cellular/DNA repair. However, adverse effects in the research and clinical processes have also been reported.

Embryonic stem cells (ESCs), derived from the blastocyst stage of early mammalian embryos, are distinguished by their ability to differentiate into any cell type and by their ability to propagate. It is these traits that makes them valuable in the scientific/medical fields. ESC are also described as having a normal karyotype, maintaining high telomerase activity, and exhibiting remarkable long-term proliferative potential.[5]

Embryonic stem cells of the inner cell mass are pluripotent, meaning they are able to differentiate to generate primitive ectoderm, which ultimately differentiates during gastrulation into all derivatives of the three primary germ layers: ectoderm, endoderm, and mesoderm. These include each of the more than 220 cell types in the adult human body. Pluripotency distinguishes embryonic stem cells from adult stem cells, which are multipotent and can only produce a limited number of cell types.

Under defined conditions, embryonic stem cells are capable of propagating indefinitely in an undifferentiated state. Conditions must either prevent the cells from clumping, or maintain an environment that supports an unspecialized state.[2] While being able to remain undifferentiated, ESCs also have the capacity, when provided with the appropriate signals, to differentiate (presumably via the initial formation of precursor cells) into nearly all mature cell phenotypes.[6]

Due to their plasticity and potentially unlimited capacity for self-renewal, embryonic stem cell therapies have been proposed for regenerative medicine and tissue replacement after injury or disease. Pluripotent stem cells have shown potential in treating a number of varying conditions, including but not limited to: spinal cord injuries, age related macular degeneration, diabetes, neurodegenerative disorders (such as Parkinson's disease), AIDS, etc.[7] In addition to their potential in regenerative medicine, embryonic stem cells provide an alternative source of tissue/organs which serves as a possible solution to the donor shortage dilemma. Not only that, but tissue/organs derived from ESCs can be made immunocompatible with the recipient. Aside from these uses, embryonic stem cells can also serve as tools for the investigation of early human development, study of genetic disease and as in vitro systems for toxicology testing.[5]

According to a 2002 article in PNAS, "Human embryonic stem cells have the potential to differentiate into various cell types, and, thus, may be useful as a source of cells for transplantation or tissue engineering."[8]

However, embryonic stem cells are not limited to cell/tissue engineering.

Current research focuses on differentiating ESCs into a variety of cell types for eventual use as cell replacement therapies (CRTs). Some of the cell types that have or are currently being developed include cardiomyocytes (CM), neurons, hepatocytes, bone marrow cells, islet cells and endothelial cells.[9] However, the derivation of such cell types from ESCs is not without obstacles, therefore current research is focused on overcoming these barriers. For example, studies are underway to differentiate ESCs in to tissue specific CMs and to eradicate their immature properties that distinguish them from adult CMs.[10]

Besides becoming an important alternative to organ transplants, ESCs are also being used in field of toxicology and as cellular screens to uncover new chemical entities (NCEs) that can be developed as small molecule drugs. Studies have shown that cardiomyocytes derived from ESCs are validated in vitro models to test drug responses and predict toxicity profiles.[9] ES derived cardiomyocytes have been shown to respond to pharmacological stimuli and hence can be used to assess cardiotoxicity like Torsades de Pointes.[17]

ESC-derived hepatocytes are also useful models that could be used in the preclinical stages of drug discovery. However, the development of hepatocytes from ESCs has proven to be challenging and this hinders the ability to test drug metabolism. Therefore, current research is focusing on establishing fully functional ESC-derived hepatocytes with stable phase I and II enzyme activity.[18]

Several new studies have started to address the concept of modeling genetic disorders with embryonic stem cells. Either by genetically manipulating the cells, or more recently, by deriving diseased cell lines identified by prenatal genetic diagnosis (PGD), modeling genetic disorders is something that has been accomplished with stem cells. This approach may very well prove invaluable at studying disorders such as Fragile-X syndrome, Cystic fibrosis, and other genetic maladies that have no reliable model system.

Yury Verlinsky, a Russian-American medical researcher who specialized in embryo and cellular genetics (genetic cytology), developed prenatal diagnosis testing methods to determine genetic and chromosomal disorders a month and a half earlier than standard amniocentesis. The techniques are now used by many pregnant women and prospective parents, especially couples who have a history of genetic abnormalities or where the woman is over the age of 35 (when the risk of genetically related disorders is higher). In addition, by allowing parents to select an embryo without genetic disorders, they have the potential of saving the lives of siblings that already had similar disorders and diseases using cells from the disease free offspring.[19]

Differentiated somatic cells and ES cells use different strategies for dealing with DNA damage. For instance, human foreskin fibroblasts, one type of somatic cell, use non-homologous end joining (NHEJ), an error prone DNA repair process, as the primary pathway for repairing double-strand breaks (DSBs) during all cell cycle stages.[20] Because of its error-prone nature, NHEJ tends to produce mutations in a cells clonal descendants.

ES cells use a different strategy to deal with DSBs.[21] Because ES cells give rise to all of the cell types of an organism including the cells of the germ line, mutations arising in ES cells due to faulty DNA repair are a more serious problem than in differentiated somatic cells. Consequently, robust mechanisms are needed in ES cells to repair DNA damages accurately, and if repair fails, to remove those cells with un-repaired DNA damages. Thus, mouse ES cells predominantly use high fidelity homologous recombinational repair (HRR) to repair DSBs.[21] This type of repair depends on the interaction of the two sister chromosomes formed during S phase and present together during the G2 phase of the cell cycle. HRR can accurately repair DSBs in one sister chromosome by using intact information from the other sister chromosome. Cells in the G1 phase of the cell cycle (i.e. after metaphase/cell division but prior the next round of replication) have only one copy of each chromosome (i.e. sister chromosomes arent present). Mouse ES cells lack a G1 checkpoint and do not undergo cell cycle arrest upon acquiring DNA damage.[22] Rather they undergo programmed cell death (apoptosis) in response to DNA damage.[23] Apoptosis can be used as a fail-safe strategy to remove cells with un-repaired DNA damages in order to avoid mutation and progression to cancer.[24] Consistent with this strategy, mouse ES stem cells have a mutation frequency about 100-fold lower than that of isogenic mouse somatic cells.[25]

On January 23, 2009, Phase I clinical trials for transplantation of oligodendrocytes (a cell type of the brain and spinal cord) derived from human ES cells into spinal cord-injured individuals received approval from the U.S. Food and Drug Administration (FDA), marking it the world's first human ES cell human trial.[26] The study leading to this scientific advancement was conducted by Hans Keirstead and colleagues at the University of California, Irvine and supported by Geron Corporation of Menlo Park, CA, founded by Michael D. West, PhD. A previous experiment had shown an improvement in locomotor recovery in spinal cord-injured rats after a 7-day delayed transplantation of human ES cells that had been pushed into an oligodendrocytic lineage.[27] The phase I clinical study was designed to enroll about eight to ten paraplegics who have had their injuries no longer than two weeks before the trial begins, since the cells must be injected before scar tissue is able to form. The researchers emphasized that the injections were not expected to fully cure the patients and restore all mobility. Based on the results of the rodent trials, researchers speculated that restoration of myelin sheathes and an increase in mobility might occur. This first trial was primarily designed to test the safety of these procedures and if everything went well, it was hoped that it would lead to future studies that involve people with more severe disabilities.[28] The trial was put on hold in August 2009 due to FDA concerns regarding a small number of microscopic cysts found in several treated rat models but the hold was lifted on July 30, 2010.[29]

In October 2010 researchers enrolled and administered ESTs to the first patient at Shepherd Center in Atlanta.[30] The makers of the stem cell therapy, Geron Corporation, estimated that it would take several months for the stem cells to replicate and for the GRNOPC1 therapy to be evaluated for success or failure.

In November 2011 Geron announced it was halting the trial and dropping out of stem cell research for financial reasons, but would continue to monitor existing patients, and was attempting to find a partner that could continue their research.[31] In 2013 BioTime (AMEX:BTX), led by CEO Dr. Michael D. West, acquired all of Geron's stem cell assets, with the stated intention of restarting Geron's embryonic stem cell-based clinical trial for spinal cord injury research.[32]

BioTime company Asterias Biotherapeutics (NYSE MKT: AST) was granted a $14.3 million Strategic Partnership Award by the California Institute for Regenerative Medicine (CIRM) to re-initiate the worlds first embryonic stem cell-based human clinical trial, for spinal cord injury. Supported by California public funds, CIRM is the largest funder of stem cell-related research and development in the world.[33]

The award provides funding for Asterias to reinitiate clinical development of AST-OPC1 in subjects with spinal cord injury and to expand clinical testing of escalating doses in the target population intended for future pivotal trials.[33]

AST-OPC1 is a population of cells derived from human embryonic stem cells (hESCs) that contains oligodendrocyte progenitor cells (OPCs). OPCs and their mature derivatives called oligodendrocytes provide critical functional support for nerve cells in the spinal cord and brain. Asterias recently presented the results from phase 1 clinical trial testing of a low dose of AST-OPC1 in patients with neurologically-complete thoracic spinal cord injury. The results showed that AST-OPC1 was successfully delivered to the injured spinal cord site. Patients followed 23 years after AST-OPC1 administration showed no evidence of serious adverse events associated with the cells in detailed follow-up assessments including frequent neurological exams and MRIs. Immune monitoring of subjects through one year post-transplantation showed no evidence of antibody-based or cellular immune responses to AST-OPC1. In four of the five subjects, serial MRI scans performed throughout the 23 year follow-up period indicate that reduced spinal cord cavitation may have occurred and that AST-OPC1 may have had some positive effects in reducing spinal cord tissue deterioration. There was no unexpected neurological degeneration or improvement in the five subjects in the trial as evaluated by the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) exam.[33]

The Strategic Partnership III grant from CIRM will provide funding to Asterias to support the next clinical trial of AST-OPC1 in subjects with spinal cord injury, and for Asterias product development efforts to refine and scale manufacturing methods to support later-stage trials and eventually commercialization. CIRM funding will be conditional on FDA approval for the trial, completion of a definitive agreement between Asterias and CIRM, and Asterias continued progress toward the achievement of certain pre-defined project milestones.[33]

The major concern with the possible transplantation of ESC into patients as therapies is their ability to form tumors including teratoma.[34] Safety issues prompted the FDA to place a hold on the first ESC clinical trial, however no tumors were observed.

The main strategy to enhance the safety of ESC for potential clinical use is to differentiate the ESC into specific cell types (e.g. neurons, muscle, liver cells) that have reduced or eliminated ability to cause tumors. Following differentiation, the cells are subjected to sorting by flow cytometry for further purification. ESC are predicted to be inherently safer than IPS cells created with genetically-integrating viral vectors because they are not genetically modified with genes such as c-Myc that are linked to cancer. Nonetheless, ESC express very high levels of the iPS inducing genes and these genes including Myc are essential for ESC self-renewal and pluripotency,[35] and potential strategies to improve safety by eliminating c-Myc expression are unlikely to preserve the cells' "stemness". However, N-myc and L-myc have been identified to induce iPS cells instead of c-myc with similar efficiency.[36]More recent protocols to induce pluripotency bypass these problems completely by using non-integrating RNA viral vectors such as sendai virus or mRNA transfection.

Due to the nature of embryonic stem cell research, there is a lot of controversial opinions on the topic. Since harvesting embryonic stem cells necessitates destroying the embryo from which those cells are obtained, the moral status of the embryo comes into question. Scientists argue that the 5-day old mass of cells is too young to achieve personhood or that the embryo, if donated from an IVF clinic (which is where labs typically acquire embryos from), would otherwise go to medical waste anyway. Opponents of ESC research counter that any embryo has the potential to become a human, therefore destroying it is murder and the embryo must be protected under the same ethical view as a developed human being.[37]

In vitro fertilization generates multiple embryos. The surplus of embryos is not clinically used or is unsuitable for implantation into the patient, and therefore may be donated by the donor with consent. Human embryonic stem cells can be derived from these donated embryos or additionally they can also be extracted from cloned embryos using a cell from a patient and a donated egg.[49] The inner cell mass (cells of interest), from the blastocyst stage of the embryo, is separated from the trophectoderm, the cells that would differentiate into extra-embryonic tissue. Immunosurgery, the process in which antibodies are bound to the trophectoderm and removed by another solution, and mechanical dissection are performed to achieve separation. The resulting inner cell mass cells are plated onto cells that will supply support. The inner cell mass cells attach and expand further to form a human embryonic cell line, which are undifferentiated. These cells are fed daily and are enzymatically or mechanically separated every four to seven days. For differentiation to occur, the human embryonic stem cell line is removed from the supporting cells to form embryoid bodies, is co-cultured with a serum containing necessary signals, or is grafted in a three-dimensional scaffold to result.[50]

Embryonic stem cells are derived from the inner cell mass of the early embryo, which are harvested from the donor mother animal. Martin Evans and Matthew Kaufman reported a technique that delays embryo implantation, allowing the inner cell mass to increase. This process includes removing the donor mother's ovaries and dosing her with progesterone, changing the hormone environment, which causes the embryos to remain free in the uterus. After 46 days of this intrauterine culture, the embryos are harvested and grown in in vitro culture until the inner cell mass forms egg cylinder-like structures, which are dissociated into single cells, and plated on fibroblasts treated with mitomycin-c (to prevent fibroblast mitosis). Clonal cell lines are created by growing up a single cell. Evans and Kaufman showed that the cells grown out from these cultures could form teratomas and embryoid bodies, and differentiate in vitro, all of which indicating that the cells are pluripotent.[41]

Gail Martin derived and cultured her ES cells differently. She removed the embryos from the donor mother at approximately 76 hours after copulation and cultured them overnight in a medium containing serum. The following day, she removed the inner cell mass from the late blastocyst using microsurgery. The extracted inner cell mass was cultured on fibroblasts treated with mitomycin-c in a medium containing serum and conditioned by ES cells. After approximately one week, colonies of cells grew out. These cells grew in culture and demonstrated pluripotent characteristics, as demonstrated by the ability to form teratomas, differentiate in vitro, and form embryoid bodies. Martin referred to these cells as ES cells.[42]

It is now known that the feeder cells provide leukemia inhibitory factor (LIF) and serum provides bone morphogenetic proteins (BMPs) that are necessary to prevent ES cells from differentiating.[51][52] These factors are extremely important for the efficiency of deriving ES cells. Furthermore, it has been demonstrated that different mouse strains have different efficiencies for isolating ES cells.[53] Current uses for mouse ES cells include the generation of transgenic mice, including knockout mice. For human treatment, there is a need for patient specific pluripotent cells. Generation of human ES cells is more difficult and faces ethical issues. So, in addition to human ES cell research, many groups are focused on the generation of induced pluripotent stem cells (iPS cells).[54]

On August 23, 2006, the online edition of Nature scientific journal published a letter by Dr. Robert Lanza (medical director of Advanced Cell Technology in Worcester, MA) stating that his team had found a way to extract embryonic stem cells without destroying the actual embryo.[55] This technical achievement would potentially enable scientists to work with new lines of embryonic stem cells derived using public funding in the USA, where federal funding was at the time limited to research using embryonic stem cell lines derived prior to August 2001. In March, 2009, the limitation was lifted.[56]

The iPSC technology was pioneered by Shinya Yamanakas lab in Kyoto, Japan, who showed in 2006 that the introduction of four specific genes encoding transcription factors could convert adult cells into pluripotent stem cells.[57] He was awarded the 2012 Nobel Prize along with Sir John Gurdon "for the discovery that mature cells can be reprogrammed to become pluripotent." [58]

In 2007 it was shown that pluripotent stem cells highly similar to embryonic stem cells can be generated by the delivery of three genes (Oct4, Sox2, and Klf4) to differentiated cells.[59] The delivery of these genes "reprograms" differentiated cells into pluripotent stem cells, allowing for the generation of pluripotent stem cells without the embryo. Because ethical concerns regarding embryonic stem cells typically are about their derivation from terminated embryos, it is believed that reprogramming to these "induced pluripotent stem cells" (iPS cells) may be less controversial. Both human and mouse cells can be reprogrammed by this methodology, generating both human pluripotent stem cells and mouse pluripotent stem cells without an embryo.[60]

This may enable the generation of patient specific ES cell lines that could potentially be used for cell replacement therapies. In addition, this will allow the generation of ES cell lines from patients with a variety of genetic diseases and will provide invaluable models to study those diseases.

However, as a first indication that the induced pluripotent stem cell (iPS) cell technology can in rapid succession lead to new cures, it was used by a research team headed by Rudolf Jaenisch of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, to cure mice of sickle cell anemia, as reported by Science journal's online edition on December 6, 2007.[61][62]

On January 16, 2008, a California-based company, Stemagen, announced that they had created the first mature cloned human embryos from single skin cells taken from adults. These embryos can be harvested for patient matching embryonic stem cells.[63]

The online edition of Nature Medicine published a study on January 24, 2005, which stated that the human embryonic stem cells available for federally funded research are contaminated with non-human molecules from the culture medium used to grow the cells.[64] It is a common technique to use mouse cells and other animal cells to maintain the pluripotency of actively dividing stem cells. The problem was discovered when non-human sialic acid in the growth medium was found to compromise the potential uses of the embryonic stem cells in humans, according to scientists at the University of California, San Diego.[65]

However, a study published in the online edition of Lancet Medical Journal on March 8, 2005 detailed information about a new stem cell line that was derived from human embryos under completely cell- and serum-free conditions. After more than 6 months of undifferentiated proliferation, these cells demonstrated the potential to form derivatives of all three embryonic germ layers both in vitro and in teratomas. These properties were also successfully maintained (for more than 30 passages) with the established stem cell lines.[66]

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Stem cell, an undifferentiated cell that can divide to produce some offspring cells that continue as stem cells and some cells that are destined to differentiate (become specialized). Stem cells are an ongoing source of the differentiated cells that make up the tissues and organs of animals and plants. There is great interest in stem cells because they have potential in the development of therapies for replacing defective or damaged cells resulting from a variety of disorders and injuries, such as Parkinson disease, heart disease, and diabetes. There are two major types of stem cells: embryonic stem cells and adult stem cells, which are also called tissue stem cells.

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cardiovascular disease: Cardiac stem cells

Cardiac stem cells, which have the ability to differentiate (specialize) into mature heart cells and therefore could be used to repair damaged or diseased heart tissue, have garnered significant interest in the development of treatments for heart disease and cardiac defects. Cardiac stem

Embryonic stem cells (often referred to as ES cells) are stem cells that are derived from the inner cell mass of a mammalian embryo at a very early stage of development, when it is composed of a hollow sphere of dividing cells (a blastocyst). Embryonic stem cells from human embryos and from embryos of certain other mammalian species can be grown in tissue culture.

The most-studied embryonic stem cells are mouse embryonic stem cells, which were first reported in 1981. This type of stem cell can be cultured indefinitely in the presence of leukemia inhibitory factor (LIF), a glycoprotein cytokine. If cultured mouse embryonic stem cells are injected into an early mouse embryo at the blastocyst stage, they will become integrated into the embryo and produce cells that differentiate into most or all of the tissue types that subsequently develop. This ability to repopulate mouse embryos is the key defining feature of embryonic stem cells, and because of it they are considered to be pluripotentthat is, able to give rise to any cell type of the adult organism. If the embryonic stem cells are kept in culture in the absence of LIF, they will differentiate into embryoid bodies, which somewhat resemble early mouse embryos at the egg-cylinder stage, with embryonic stem cells inside an outer layer of endoderm. If embryonic stem cells are grafted into an adult mouse, they will develop into a type of tumour called a teratoma, which contains a variety of differentiated tissue types.

Mouse embryonic stem cells are widely used to create genetically modified mice. This is done by introducing new genes into embryonic stem cells in tissue culture, selecting the particular genetic variant that is desired, and then inserting the genetically modified cells into mouse embryos. The resulting chimeric mice are composed partly of host cells and partly of the donor embryonic stem cells. As long as some of the chimeric mice have germ cells (sperm or eggs) that have been derived from the embryonic stem cells, it is possible to breed a line of mice that have the same genetic constitution as the embryonic stem cells and therefore incorporate the genetic modification that was made in vitro. This method has been used to produce thousands of new genetic lines of mice. In many such genetic lines, individual genes have been ablated in order to study their biological function; in others, genes have been introduced that have the same mutations that are found in various human genetic diseases. These mouse models for human disease are used in research to investigate both the pathology of the disease and new methods for therapy.

Extensive experience with mouse embryonic stem cells made it possible for scientists to grow human embryonic stem cells from early human embryos, and the first human stem cell line was created in 1998. Human embryonic stem cells are in many respects similar to mouse embryonic stem cells, but they do not require LIF for their maintenance. The human embryonic stem cells form a wide variety of differentiated tissues in vitro, and they form teratomas when grafted into immunosuppressed mice. It is not known whether the cells can colonize all the tissues of a human embryo, but it is presumed from their other properties that they are indeed pluripotent cells, and they therefore are regarded as a possible source of differentiated cells for cell therapythe replacement of a patients defective cell type with healthy cells. Large quantities of cells, such as dopamine-secreting neurons for the treatment of Parkinson disease and insulin-secreting pancreatic beta cells for the treatment of diabetes, could be produced from embryonic stem cells for cell transplantation. Cells for this purpose have previously been obtainable only from sources in very limited supply, such as the pancreatic beta cells obtained from the cadavers of human organ donors.

The use of human embryonic stem cells evokes ethical concerns, because the blastocyst-stage embryos are destroyed in the process of obtaining the stem cells. The embryos from which stem cells have been obtained are produced through in vitro fertilization, and people who consider preimplantation human embryos to be human beings generally believe that such work is morally wrong. Others accept it because they regard the blastocysts to be simply balls of cells, and human cells used in laboratories have not previously been accorded any special moral or legal status. Moreover, it is known that none of the cells of the inner cell mass are exclusively destined to become part of the embryo itselfall of the cells contribute some or all of their cell offspring to the placenta, which also has not been accorded any special legal status. The divergence of views on this issue is illustrated by the fact that the use of human embryonic stem cells is allowed in some countries and prohibited in others.

In 2009 the U.S. Food and Drug Administration approved the first clinical trial designed to test a human embryonic stem cell-based therapy, but the trial was halted in late 2011 because of a lack of funding and a change in lead American biotech company Gerons business directives. The therapy to be tested was known as GRNOPC1, which consisted of progenitor cells (partially differentiated cells) that, once inside the body, matured into neural cells known as oligodendrocytes. The oligodendrocyte progenitors of GRNOPC1 were derived from human embryonic stem cells. The therapy was designed for the restoration of nerve function in persons suffering from acute spinal cord injury.

Embryonic germ (EG) cells, derived from primordial germ cells found in the gonadal ridge of a late embryo, have many of the properties of embryonic stem cells. The primordial germ cells in an embryo develop into stem cells that in an adult generate the reproductive gametes (sperm or eggs). In mice and humans it is possible to grow embryonic germ cells in tissue culture with the appropriate growth factorsnamely, LIF and another cytokine called fibroblast growth factor.

Some tissues in the adult body, such as the epidermis of the skin, the lining of the small intestine, and bone marrow, undergo continuous cellular turnover. They contain stem cells, which persist indefinitely, and a much larger number of transit amplifying cells, which arise from the stem cells and divide a finite number of times until they become differentiated. The stem cells exist in niches formed by other cells, which secrete substances that keep the stem cells alive and active. Some types of tissue, such as liver tissue, show minimal cell division or undergo cell division only when injured. In such tissues there is probably no special stem-cell population, and any cell can participate in tissue regeneration when required.

The epidermis of the skin contains layers of cells called keratinocytes. Only the basal layer, next to the dermis, contains cells that divide. A number of these cells are stem cells, but the majority are transit amplifying cells. The keratinocytes slowly move outward through the epidermis as they mature, and they eventually die and are sloughed off at the surface of the skin. The epithelium of the small intestine forms projections called villi, which are interspersed with small pits called crypts. The dividing cells are located in the crypts, with the stem cells lying near the base of each crypt. Cells are continuously produced in the crypts, migrate onto the villi, and are eventually shed into the lumen of the intestine. As they migrate, they differentiate into the cell types characteristic of the intestinal epithelium.

Bone marrow contains cells called hematopoietic stem cells, which generate all the cell types of the blood and the immune system. Hematopoietic stem cells are also found in small numbers in peripheral blood and in larger numbers in umbilical cord blood. In bone marrow, hematopoietic stem cells are anchored to osteoblasts of the trabecular bone and to blood vessels. They generate progeny that can become lymphocytes, granulocytes, red blood cells, and certain other cell types, depending on the balance of growth factors in their immediate environment.

Work with experimental animals has shown that transplants of hematopoietic stem cells can occasionally colonize other tissues, with the transplanted cells becoming neurons, muscle cells, or epithelia. The degree to which transplanted hematopoietic stem cells are able to colonize other tissues is exceedingly small. Despite this, the use of hematopoietic stem cell transplants is being explored for conditions such as heart disease or autoimmune disorders. It is an especially attractive option for those opposed to the use of embryonic stem cells.

Bone marrow transplants (also known as bone marrow grafts) represent a type of stem cell therapy that is in common use. They are used to allow cancer patients to survive otherwise lethal doses of radiation therapy or chemotherapy that destroy the stem cells in bone marrow. For this procedure, the patients own marrow is harvested before the cancer treatment and is then reinfused into the body after treatment. The hematopoietic stem cells of the transplant colonize the damaged marrow and eventually repopulate the blood and the immune system with functional cells. Bone marrow transplants are also often carried out between individuals (allograft). In this case the grafted marrow has some beneficial antitumour effect. Risks associated with bone marrow allografts include rejection of the graft by the patients immune system and reaction of immune cells of the graft against the patients tissues (graft-versus-host disease).

Bone marrow is a source for mesenchymal stem cells (sometimes called marrow stromal cells, or MSCs), which are precursors to non-hematopoietic stem cells that have the potential to differentiate into several different types of cells, including cells that form bone, muscle, and connective tissue. In cell cultures, bone-marrow-derived mesenchymal stem cells demonstrate pluripotency when exposed to substances that influence cell differentiation. Harnessing these pluripotent properties has become highly valuable in the generation of transplantable tissues and organs. In 2008 scientists used mesenchymal stem cells to bioengineer a section of trachea that was transplanted into a woman whose upper airway had been severely damaged by tuberculosis. The stem cells were derived from the womans bone marrow, cultured in a laboratory, and used for tissue engineering. In the engineering process, a donor trachea was stripped of its interior and exterior cell linings, leaving behind a trachea scaffold of connective tissue. The stem cells derived from the recipient were then used to recolonize the interior of the scaffold, and normal epithelial cells, also isolated from the recipient, were used to recolonize the exterior of the trachea. The use of the recipients own cells to populate the trachea scaffold prevented immune rejection and eliminated the need for immunosuppression therapy. The transplant, which was successful, was the first of its kind.

Research has shown that there are also stem cells in the brain. In mammals very few new neurons are formed after birth, but some neurons in the olfactory bulbs and in the hippocampus are continually being formed. These neurons arise from neural stem cells, which can be cultured in vitro in the form of neurospheressmall cell clusters that contain stem cells and some of their progeny. This type of stem cell is being studied for use in cell therapy to treat Parkinson disease and other forms of neurodegeneration or traumatic damage to the central nervous system.

Following experiments in animals, including those used to create Dolly the sheep, there has been much discussion about the use of somatic cell nuclear transfer (SCNT) to create pluripotent human cells. In SCNT the nucleus of a somatic cell (a fully differentiated cell, excluding germ cells), which contains the majority of the cells DNA (deoxyribonucleic acid), is removed and transferred into an unfertilized egg cell that has had its own nuclear DNA removed. The egg cell is grown in culture until it reaches the blastocyst stage. The inner cell mass is then removed from the egg, and the cells are grown in culture to form an embryonic stem cell line (generations of cells originating from the same group of parent cells). These cells can then be stimulated to differentiate into various types of cells needed for transplantation. Since these cells would be genetically identical to the original donor, they could be used to treat the donor with no problems of immune rejection. Scientists generated human embryonic stem cells successfully from SCNT human embryos for the first time in 2013.

While promising, the generation and use of SCNT-derived embryonic stem cells is controversial for several reasons. One is that SCNT can require more than a dozen eggs before one egg successfully produces embryonic stem cells. Human eggs are in short supply, and there are many legal and ethical problems associated with egg donation. There are also unknown risks involved with transplanting SCNT-derived stem cells into humans, because the mechanism by which the unfertilized egg is able to reprogram the nuclear DNA of a differentiated cell is not entirely understood. In addition, SCNT is commonly used to produce clones of animals (such as Dolly). Although the cloning of humans is currently illegal throughout the world, the egg cell that contains nuclear DNA from an adult cell could in theory be implanted into a womans uterus and come to term as an actual cloned human. Thus, there exists strong opposition among some groups to the use of SCNT to generate human embryonic stem cells.

Due to the ethical and moral issues surrounding the use of embryonic stem cells, scientists have searched for ways to reprogram adult somatic cells. Studies of cell fusion, in which differentiated adult somatic cells grown in culture with embryonic stem cells fuse with the stem cells and acquire embryonic stem-cell-like properties, led to the idea that specific genes could reprogram differentiated adult cells. An advantage of cell fusion is that it relies on existing embryonic stem cells instead of eggs. However, fused cells stimulate an immune response when transplanted into humans, which leads to transplant rejection. As a result, research has become increasingly focused on the genes and proteins capable of reprogramming adult cells to a pluripotent state. In order to make adult cells pluripotent without fusing them to embryonic stem cells, regulatory genes that induce pluripotency must be introduced into the nuclei of adult cells. To do this, adult cells are grown in cell culture, and specific combinations of regulatory genes are inserted into retroviruses (viruses that convert RNA [ribonucleic acid] into DNA), which are then introduced to the culture medium. The retroviruses transport the RNA of the regulatory genes into the nuclei of the adult cells, where the genes are then incorporated into the DNA of the cells. About 1 out of every 10,000 cells acquires embryonic stem cell properties. Although the mechanism is still uncertain, it is clear that some of the genes confer embryonic stem cell properties by means of the regulation of numerous other genes. Adult cells that become reprogrammed in this way are known as induced pluripotent stem cells (iPS).

Similar to embryonic stem cells, induced pluripotent stem cells can be stimulated to differentiate into select types of cells that could in principle be used for disease-specific treatments. In addition, the generation of induced pluripotent stem cells from the adult cells of patients affected by genetic diseases can be used to model the diseases in the laboratory. For example, in 2008 researchers isolated skin cells from a child with an inherited neurological disease called spinal muscular atrophy and then reprogrammed these cells into induced pluripotent stem cells. The reprogrammed cells retained the disease genotype of the adult cells and were stimulated to differentiate into motor neurons that displayed functional insufficiencies associated with spinal muscular atrophy. By recapitulating the disease in the laboratory, scientists were able to study closely the cellular changes that occurred as the disease progressed. Such models promise not only to improve scientists understanding of genetic diseases but also to facilitate the development of new therapeutic strategies tailored to each type of genetic disease.

In 2009 scientists successfully generated retinal cells of the human eye by reprogramming adult skin cells. This advance enabled detailed investigation of the embryonic development of retinal cells and opened avenues for the generation of novel therapies for eye diseases. The production of retinal cells from reprogrammed skin cells may be particularly useful in the treatment of retinitis pigmentosa, which is characterized by the progressive degeneration of the retina, eventually leading to night blindness and other complications of vision. Although retinal cells also have been produced from human embryonic stem cells, induced pluripotency represents a less controversial approach. Scientists have also explored the possibility of combining induced pluripotent stem cell technology with gene therapy, which would be of value particularly for patients with genetic disease who would benefit from autologous transplantation.

Researchers have also been able to generate cardiac stem cells for the treatment of certain forms of heart disease through the process of dedifferentiation, in which mature heart cells are stimulated to revert to stem cells. The first attempt at the transplantation of autologous cardiac stem cells was performed in 2009, when doctors isolated heart tissue from a patient, cultured the tissue in a laboratory, stimulated cell dedifferentiation, and then reinfused the cardiac stem cells directly into the patients heart. A similar study involving 14 patients who underwent cardiac bypass surgery followed by cardiac stem cell transplantation was reported in 2011. More than three months after stem cell transplantation, the patients experienced a slight but detectable improvement in heart function.

Patient-specific induced pluripotent stem cells and dedifferentiated cells are highly valuable in terms of their therapeutic applications because they are unlikely to be rejected by the immune system. However, before induced pluripotent stem cells can be used to treat human diseases, researchers must find a way to introduce the active reprogramming genes without using retroviruses, which can cause diseases such as leukemia in humans. A possible alternative to the use of retroviruses to transport regulatory genes into the nuclei of adult cells is the use of plasmids, which are less tumourigenic than viruses.

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Stem cell facts

What are stem cells?

Stem cells are cells that have the potential to develop into many different or specialized cell types. Stem cells can be thought of as primitive, "unspecialized" cells that are able to divide and become specialized cells of the body such as liver cells, muscle cells, blood cells, and other cells with specific functions. Stem cells are referred to as "undifferentiated" cells because they have not yet committed to a developmental path that will form a specific tissue or organ. The process of changing into a specific cell type is known as differentiation. In some areas of the body, stem cells divide regularly to renew and repair the existing tissue. The bone marrow and gastrointestinal tract are examples of areas in which stem cells function to renew and repair tissue.

The best and most readily understood example of a stem cell in humans is that of the fertilized egg, or zygote. A zygote is a single cell that is formed by the union of a sperm and ovum. The sperm and the ovum each carry half of the genetic material required to form a new individual. Once that single cell or zygote starts dividing, it is known as an embryo. One cell becomes two, two become four, four become eight, eight become sixteen, and so on, doubling rapidly until it ultimately grows into an entire sophisticated organism composed of many different kinds of specialized cells. That organism, a person, is an immensely complicated structure consisting of many, many, billions of cells with functions as diverse as those of your eyes, your heart, your immune system, the color of your skin, your brain, etc. All of the specialized cells that make up these body systems are descendants of the original zygote, a stem cell with the potential to ultimately develop into all kinds of body cells. The cells of a zygote are totipotent, meaning that they have the capacity to develop into any type of cell in the body.

The process by which stem cells commit to become differentiated, or specialized, cells is complex and involves the regulation of gene expression. Research is ongoing to further understand the molecular events and controls necessary for stem cells to become specialized cell types.

Stem Cells:One of the human body's master cells, with the ability to grow into any one of the body's more than 200 cell types.

All stem cells are unspecialized (undifferentiated) cells that are characteristically of the same family type (lineage). They retain the ability to divide throughout life and give rise to cells that can become highly specialized and take the place of cells that die or are lost.

Stem cells contribute to the body's ability to renew and repair its tissues. Unlike mature cells, which are permanently committed to their fate, stem cells can both renew themselves as well as create new cells of whatever tissue they belong to (and other tissues).

Why are stem cells important?

Stem cells represent an exciting area in medicine because of their potential to regenerate and repair damaged tissue. Some current therapies, such as bone marrow transplantation, already make use of stem cells and their potential for regeneration of damaged tissues. Other therapies that are under investigation involve transplanting stem cells into a damaged body part and directing them to grow and differentiate into healthy tissue.

Embryonic stem cells

During the early stages of embryonic development the cells remain relatively undifferentiated (immature) and appear to possess the ability to become, or differentiate, into almost any tissue within the body. For example, cells taken from one section of an embryo that might have become part of the eye can be transferred into another section of the embryo and could develop into blood, muscle, nerve, or liver cells.

Cells in the early embryonic stage are totipotent (see above) and can differentiate to become any type of body cell. After about seven days, the zygote forms a structure known as a blastocyst, which contains a mass of cells that eventually become the fetus, as well as trophoblastic tissue that eventually becomes the placenta. If cells are taken from the blastocyst at this stage, they are known as pluripotent, meaning that they have the capacity to become many different types of human cells. Cells at this stage are often referred to as blastocyst embryonic stem cells. When any type of embryonic stem cells is grown in culture in the laboratory, they can divide and grow indefinitely. These cells are then known as embryonic stem cell lines.

Fetal stem cells

The embryo is referred to as a fetus after the eighth week of development. The fetus contains stem cells that are pluripotent and eventually develop into the different body tissues in the fetus.

Adult stem cells

Adult stem cells are present in all humans in small numbers. The adult stem cell is one of the class of cells that we have been able to manipulate quite effectively in the bone marrow transplant arena over the past 30 years. These are stem cells that are largely tissue-specific in their location. Rather than typically giving rise to all of the cells of the body, these cells are capable of giving rise only to a few types of cells that develop into a specific tissue or organ. They are therefore known as multipotent stem cells. Adult stem cells are sometimes referred to as somatic stem cells.

The best characterized example of an adult stem cell is the blood stem cell (the hematopoietic stem cell). When we refer to a bone marrow transplant, a stem cell transplant, or a blood transplant, the cell being transplanted is the hematopoietic stem cell, or blood stem cell. This cell is a very rare cell that is found primarily within the bone marrow of the adult.

One of the exciting discoveries of the last years has been the overturning of a long-held scientific belief that an adult stem cell was a completely committed stem cell. It was previously believed that a hematopoietic, or blood-forming stem cell, could only create other blood cells and could never become another type of stem cell. There is now evidence that some of these apparently committed adult stem cells are able to change direction to become a stem cell in a different organ. For example, there are some models of bone marrow transplantation in rats with damaged livers in which the liver partially re-grows with cells that are derived from transplanted bone marrow. Similar studies can be done showing that many different cell types can be derived from each other. It appears that heart cells can be grown from bone marrow stem cells, that bone marrow cells can be grown from stem cells derived from muscle, and that brain stem cells can turn into many types of cells.

Peripheral blood stem cells

Most blood stem cells are present in the bone marrow, but a few are present in the bloodstream. This means that these so-called peripheral blood stem cells (PBSCs) can be isolated from a drawn blood sample. The blood stem cell is capable of giving rise to a very large number of very different cells that make up the blood and immune system, including red blood cells, platelets, granulocytes, and lymphocytes.

All of these very different cells with very different functions are derived from a common, ancestral, committed blood-forming (hematopoietic), stem cell.

Umbilical cord stem cells

Blood from the umbilical cord contains some stem cells that are genetically identical to the newborn. Like adult stem cells, these are multipotent stem cells that are able to differentiate into certain, but not all, cell types. For this reason, umbilical cord blood is often banked, or stored, for possible future use should the individual require stem cell therapy.

Induced pluripotent stem cells

Induced pluripotent stem cells (iPSCs) were first created from human cells in 2007. These are adult cells that have been genetically converted to an embryonic stem celllike state. In animal studies, iPSCs have been shown to possess characteristics of pluripotent stem cells. Human iPSCs can differentiate and become multiple different fetal cell types. iPSCs are valuable aids in the study of disease development and drug treatment, and they may have future uses in transplantation medicine. Further research is needed regarding the development and use of these cells.

Why is there controversy surrounding the use of stem cells?

Embryonic stem cells and embryonic stem cell lines have received much public attention concerning the ethics of their use or non-use. Clearly, there is hope that a large number of treatment advances could occur as a result of growing and differentiating these embryonic stem cells in the laboratory. It is equally clear that each embryonic stem cell line has been derived from a human embryo created through in-vitro fertilization (IVF) or through cloning technologies, with all the attendant ethical, religious, and philosophical problems, depending upon one's perspective.

What are some stem cell therapies that are currently available?

Routine use of stem cells in therapy has been limited to blood-forming stem cells (hematopoietic stem cells) derived from bone marrow, peripheral blood, or umbilical cord blood. Bone marrow transplantation is the most familiar form of stem cell therapy and the only instance of stem cell therapy in common use. It is used to treat cancers of the blood cells (leukemias) and other disorders of the blood and bone marrow.

In bone marrow transplantation, the patient's existing white blood cells and bone marrow are destroyed using chemotherapy and radiation therapy. Then, a sample of bone marrow (containing stem cells) from a healthy, immunologically matched donor is injected into the patient. The transplanted stem cells populate the recipient's bone marrow and begin producing new, healthy blood cells.

Umbilical cord blood stem cells and peripheral blood stem cells can also be used instead of bone marrow samples to repopulate the bone marrow in the process of bone marrow transplantation.

In 2009, the California-based company Geron received clearance from the U. S. Food and Drug Administration (FDA) to begin the first human clinical trial of cells derived from human embryonic stem cells in the treatment of patients with acute spinal cord injury.

What are experimental treatments using stem cells and possible future directions for stem cell therapy?

Stem cell therapy is an exciting and active field of biomedical research. Scientists and physicians are investigating the use of stem cells in therapies to treat a wide variety of diseases and injuries. For a stem cell therapy to be successful, a number of factors must be considered. The appropriate type of stem cell must be chosen, and the stem cells must be matched to the recipient so that they are not destroyed by the recipient's immune system. It is also critical to develop a system for effective delivery of the stem cells to the desired location in the body. Finally, devising methods to "switch on" and control the differentiation of stem cells and ensure that they develop into the desired tissue type is critical for the success of any stem cell therapy.

Researchers are currently examining the use of stem cells to regenerate damaged or diseased tissue in many conditions, including those listed below.

References

REFERENCE:

"Stem Cell Information." National Institutes of Health.

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