"Signs of cancer can appear long before diagnosis," reports The Guardian.

Most cells in the body divide and reproduce constantly, picking up replication errors in their DNA over time as we age. Many of these errors may be harmless, but some can cause or increase the risk of cancer.

Cancers begin when harmful errors, or mutations, cause our cells to divide in an uncontrolled way. It's usually impossible to tell if this is happening, until the cancer starts to cause physical signs or symptoms.

In this new study, an international team of researchers sequenced the genomes (the entire DNA and genetic material) of 2,658 tumour samples.

They used the information to work out the order in which mutations and copying of mutations happened, because usually more than one mutation is needed before cells become cancerous. The researchers then modelled how different types of cancer develop over time.

They found that harmful mutations for some types of cancer, such as ovarian cancer, characteristically happen very early, in some cases decades before people have any physical signs of the disease. The findings raise hopes that some cancers could be detected and treated much earlier.

However, at present it's not clear whether this research could lead to a cancer screening system based on checking for "genetic early warning signs", both in terms of effectiveness and feasibility.

At present, the best way to detect cancer early is to be alert to the possible signs and symptoms, attend cancer screening when invited, and know about your family history of the disease.

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The research was carried out by the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, an enormous collaboration between hundreds of scientists from 4 continents. 46 scientists worked on this particular paper, from 38 universities or research institutes.

The PCAWG group published 6 papers this week, but we're focusing on just 1, which looked at the way cancers evolve over time. The study was published in the peer-reviewed journal Nature on an open-access basis, so it is free to read online.

The Guardian, BBC News and Mail Online focused on the discovery that DNA changes to cells may happen many years before cancer can currently be diagnosed, and the reporting was generally accurate.

This was a modelling study, using data from the whole genome sequencing of 2,658 cancers to reconstruct the likely evolution of DNA in these cancers over time. The study helps scientists to better understand how cancers begin and evolve.

However, at this stage, the results cannot be used to test for cancers in people.

A team of scientists worldwide worked with 2,778 samples of cancers, taken from 2,658 people with cancer. Some people gave just 1 sample, while others gave a sample of newly diagnosed primary tumours, and later, a sample of a metastatic cancer (when cancer has spread to another part of the body). 38 cancer types were represented in the samples.

The scientists carried out whole genome sequencing of the samples. This showed where DNA mutations arose, and whether they had been copied and duplicated as more DNA changes accumulated.

Researchers could look for so-called "driver" mutations, which are known to be linked to cancer, and see whether they happened early or late in the cancer's evolution.

They used this information to model a typical "life history" for each of the 38 types of cancer. This showed whether important mutations happened early or late in the cancer's development. They then estimated how that mapped against a person's life. For example, whether cancer-causing mutations happened a short time before cancer was diagnosed, or whether they had been present for years or decades before cancer was detected.

The researchers found that the time between cancer-driving mutations and diagnosis varies a lot between cancers. Some (such as liver and cervical cancer) happen 1 to 5 years before the cancer was diagnosed. By contrast, ovarian cancers showed significant mutations 10 to 40 years before diagnosis. This suggests the original mutations that lead to some adult cancers could happen during childhood or adolescence.

Other results included:

The researchers said: "Our study sheds light on the typical timescale of tumour development, with initial driver events seemingly occurring up to decades before diagnosis." They say the results "highlight opportunities for early cancer detection."

This study represents an enormous achievement by many scientists working together to find out more about how cancers develop over time. This type of work is likely to be important in developing future tests for cancers, and possibly new treatments that can target cancers at a very early stage.

However, the study does not change how cancer is diagnosed or treated at present. It can take years before early-stage research like this leads to changes in clinical practice.

As one of the scientists involved in the study told journalists, the idea of being able to target mutations by doing blood tests during childhood, then eliminate dangerous mutations, is "science fiction".

This research is very complex and, as with all modelling, it relies on some assumptions about the time it takes for mutations to arise, be duplicated and copied. The accuracy of the findings will depend on the accuracy of these assumptions.

All samples in the study came from people who had developed cancer. It would be interesting to compare findings with non-cancerous tissue samples from these people, or samples from people who did not develop cancer.

It's good news that DNA sequencing technology now allows scientists to work on such a large scale, and that theyre able to work together to find out more detail about the way that cancers evolve. This type of work could make a big difference to the way doctors approach cancer in future.

Analysis by BazianEdited by NHS Website

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People who develop Parkinson's disease at a younger age (before age 50) may have malfunctioning brain cells at birth, according to a study that also identified a drug that may help these patients.

At least 500,000 people in the United States are diagnosed with Parkinson's each year. Most are 60 or older at diagnosis, but about 10% are between 21 and 50.

Parkinson's is a neurological disease that occurs when brain neurons that make dopamine become impaired or die. Dopamine helps coordinate muscle movement.

Symptoms get worse over time and include slow gait, rigidity, tremors, and loss of balance. There is currently no cure.

"Young-onset Parkinson's is especially heartbreaking because it strikes people at the prime of life," said study co-author Dr. Michele Tagliati, director of the Movement Disorders Program at Cedars-Sinai Medical Center in Los Angeles.

"This exciting new research provides hope that one day we may be able to detect and take early action to prevent this disease in at-risk individuals," he said in a hospital news release.

For the study, Tagliati and colleagues generated special stem cells from the cells of patients with young-onset Parkinson's disease. These stem cells can produce any cell type of the human body. Researchers used them to produce dopamine neurons from each patient and analyzed those neurons in the lab.

The dopamine neurons showed two key abnormalities: buildup of a protein called alpha-synuclein, which occurs in most forms of Parkinson's disease; and malfunctioning lysosomes, structures that act as "trash cans" for the cell to break down and dispose of proteins. This malfunction could result in a buildup of alpha-synuclein, the researchers said.

"Our technique gave us a window back in time to see how well the dopamine neurons might have functioned from the very start of a patient's life," said senior author Clive Svendsen, director of the Cedars Sinai Board of Governors Regenerative Medicine Institute.

"What we are seeing using this new model are the very first signs of young-onset Parkinson's," Svendsen said in the release. "It appears that dopamine neurons in these individuals may continue to mishandle alpha-synuclein over a period of 20 or 30 years, causing Parkinson's symptoms to emerge."

The study was published Jan. 27 in the journalNature Medicine.

The researchers also tested drugs that might reverse the neuron abnormalities. A drug called PEP005 already approved by the U.S. Food and Drug Administration for treating precancers of the skin reduced elevated levels of alpha-synuclein both in mice and in dopamine neurons in the lab.

The investigators plan to determine how PEP005, which is available in gel form, might be delivered to the brain to potentially treat or prevent young-onset Parkinson's.

They also want to find out whether the abnormalities in neurons of young-onset Parkinson's patients also exist in other forms of Parkinson's.

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When talented rugby player George Thompson went to see his doctor with a suspected match-related injury, the last thing he expected to hear was the word 'cancer'.

George Thompson had been playing rugby since the age of six, spending most of his young sporting career at Devonport Services RFC, representing Devon U15s, captaining Devon U16s and Plymouth Albion U18s, before joining the Exeter Chiefs Academy.

The 17-year-old, from Saltash, was set to join his local club, Saltash RFC, but in a devastating and unexpected blow has had to give up the sport he loves after being diagnosed with Neuroblastoma.

The rare type of cancer mostly affects babies and young children, but very occasionally is found in adolescents.

George, who is in his second year of a gas engineering apprenticeship with Plymouth Community Homes, began suffering with lower back pain and was originally told that it was believed he had ankylosing spondylitis - a long-term condition which means the spine and other areas of the body become inflamed.

But after numerous scans and tests, he was told he had the rare cancer, which had also spread to his bones and bone marrow.

He has now been transferred to Bristol Royal Hospital for children where he is undergoing chemotherapy.

George now has a 12-month plan which will include surgery, chemotherapy, blood transfusions, radiotherapy and immunotherapy.

More than 13,800 has been raised on a crowdfunding page - which you can donate to here - set up by George's auntie, Catherine Arris.

George's sister, Rosie, said the "response has been overwhelming".

She said the money will help herself, her mother Julie and father, Martin with travel costs and subsidise their lost income whilst frequently making back-and-forth trips from Cornwall to Bristol, to ensure that they are with George throughout "the intense treatment period".

Rosie said: "This will also enable George to have some quality downtime away from the hospital ward when he is well enough in-between treatments.

"It is important to us that we maintain as normal a family life as possible throughout the difficult months that lie ahead and this is now being made possible by the generosity of so many people.

"There are not enough words to thank each and every person who is supporting us."

Rosie explained that any money which remains at the end of George's treatment will be donated to Clic Sargent, The Teenage Cancer Trust and Neuroblastoma UK.

"These charities are already looking after us, providing accommodation and various support," she said.

George has already undergone four blood transfusions and it is likely he will receive further transfusions.

Rosie said: "We are all signing up to donate blood and would encourage as many people as possible to follow suit. We have seen first hand how important blood donations are.

"In such a short space of time we have been amazed by the generosity and heartfelt messages of support.

"Georges fun loving character and caring nature has been recognised by so many people, some who have never met George."

There are a number of plans for fund-raising events to take place during Georges treatment, to raise money for Clic Sargent and the Teenage Cancer Trust.

Plymouth Community Homes is set to arrange an event, as well as a team named 'Run For George' which has entered into the Mudstock Run on June 27, 2020, supported by BH Fitness.

There is also a fund-raising rugby match on April 18, 2020, which has been organised by George's uncle, Richard Thompson.

If you are interested in this story, you may be interested in the crowdfunder for the Plymouth man diagnosed with testicular cancer at just 21 years old.

Neuroblastoma is a rare type of cancer that mostly affects babies and young children.

It develops from specialised nerve cells (neuroblasts) left behind from a baby's development in the womb.

Neuroblastoma most commonly occurs in 1 of the adrenal glands situated above the kidneys, or in the nerve tissue that runs alongside the spinal cord in the neck, chest,tummy or pelvis.

It can spread to other organs, such as the bone marrow, bone, lymph nodes, liver and skin.

It affects around 100 children each year in the UK and is most common in children under the age of 5.

The cause is unknown. There are very rare cases where children in the same family are affected, but generally neuroblastoma does not run in families.

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The symptoms of neuroblastoma vary depending on where the cancer is and whether it's spread.

The early symptoms can be vague and hard to spot, and can easily be mistaken for those of more common childhood conditions.

Symptoms can include:

See a GP or contactNHS 111if you're worried your child might be seriously ill.

A number of tests may be carried out if it's thought your child could have neuroblastoma.

These tests may include:

Once these tests have been completed, it'll usually be possible to confirm if the diagnosis is neuroblastoma and determine what stage it is.

As with most cancers, neuroblastoma is given a stage. This indicates if it's spread and, if so, how far.

The staging system used for neuroblastoma is:

Knowing the stage of your child's neuroblastoma will allow doctors to decide which treatment is best.

Some babies and infants less than 18 months old with either stage L1 or Ms neuroblastoma who have no symptoms may not need any treatment, as the cancer can sometimes go away on its own.

The main treatments for neuroblastoma are:

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Like most medical students, I struggled to memorize the Krebs cycle, the complex energy-producing process that takes place in the body's mitochondria. Rote learning of Sir Hans Krebs' eponymous cascade of reactions persists and has been cited as a waste of time in modern medical education. However, it looks like that specialized knowledge about mitochondrial structure and function may finally come in handy in the clinic.

Advances in genetics have contributed to improved diagnostic accuracy of a diverse spectrum of mitochondrial disorders. Respiratory chain, nuclear gene, and mitochondrial proteome mutations can lead to multisystem or organ-specific dysfunction.

A new potential treatment for mitochondrial disorders, elamipretide, has received orphan drug designation from the US Food and Drug Administration (FDA) and is in clinical trials sponsored by Stealth Biotherapeutics. [Dr Wilner has consulted for Stealth Biotherapeutics.] Recently I had the opportunity to interview Hilary Vernon, MD, PhD, associate professor of genetic medicine at Johns Hopkins University, Baltimore, Maryland, and an expert on mitochondrial disorders. Dr Vernon discussed her research on elamipretide as a treatment for Barth syndrome, a rare form of mitochondrial disease.

I am the director of the Mitochondrial Medicine Center at Johns Hopkins Hospital. I work with individuals from infancy through adulthood who have mitochondrial conditions. I became interested in this particular area when I was early in my pediatrics/genetics residency at Johns Hopkins and saw the toll that mitochondrial disorders took on patients' lives and the limited effective therapies. At that point, I decided to focus on patient care and research in this area.

Mitochondrial disorders can be difficult to recognize because of their inherent multisystem nature and variable presentations (even between affected members of the same family). However, there are several considerations that should raise a clinician's suspicion for a mitochondrial condition. Ascertaining a family history of disease inheritance through the maternal line can raise the suspicion for a mitochondrial DNA disorder. Identification of a combination of medical issues in different organ systems that are seemingly unrelated in an individual (ie, optic atrophy and muscle weakness or diabetes and hearing loss) can also raise suspicion for a mitochondrial condition.

Due to the nature of mitochondria as the major energy producers of the cells, high-energy-requiring tissues such as the brain and the muscles are often affected. Perhaps the best known mitochondrial diseases to neurologists are MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke) as well as MERFF (myoclonic epilepsy with ragged red fibers). There is a nice body of literature on the effects of arginine and citrulline in modifying stroke-like episodes in MELAS, and this is a therapy that is in current practice.

Mitochondria are complex organelles whose structure and function are encoded in hundreds of genes originating from both the nucleus of the cell and the mitochondria themselves. Mitochondria have many key roles in cellular function, including energy production through the respiratory chain, coordination of apoptosis, nitrogen metabolism, fatty acid oxidation, and much more.

Various cofactors and vitamins can be employed to improve mitochondrial function for different reasons. For example, if a specific enzyme is dysfunctional, supplying the cofactor for that enzyme may improve its function (ie, pyruvate dehydrogenase and thiamine). Antioxidants have also been considered to help reduce the oxidant load that could potentially cause ongoing damage to the mitochondrial membrane resulting from respiratory chain dysfunction (ie, coenzyme Q-10).

It is important to remember that the highest number of individual mitochondrial disorders result from mutations in genes located in the nuclear DNA. For example, the TAZ gene that is abnormal in Barth syndrome is a nuclear gene located on the X chromosome. These genes are amenable to the "regular" approaches to gene therapy.

Targeting mitochondrial DNA for gene therapy requires a different set of approaches because the gene delivery has to overcome the barrier of the mitochondrial membranes. However, research is ongoing to overcome these obstacles.

Barth syndrome is a very rare genetic X-linked disorder that usually only affects males. The genetic defect leads to an abnormal composition of cardiolipin on the inner mitochondrial membrane. Cardiolipin is an important phospholipid involved in many mitochondrial functions, including organization of inner mitochondrial membrane cristae, involvement in apoptosis, and organization of the respiratory chain (which is responsible for producing ATP via the process of oxidative phosphorylation), and many of these functions are abnormal in Barth syndrome. Individuals with Barth syndrome typically have early-onset cardiomyopathy, myopathy, intermittent neutropenia, fatigue, poor early growth, among other health concerns.

Early in my post-residency career, I followed several patients with Barth syndrome and was quickly welcomed into the Barth syndrome community by the families and the Barth Syndrome Foundation. From there, I founded the only interdisciplinary Barth syndrome clinic in the US and began to focus a significant amount of my clinical and laboratory research on this condition.

Most commonly, these individuals come to medical attention because of cardiomyopathy, but a minority of patients do come to attention due to repeated infections and neutropenia. Patients were identified for study participation through the Barth Syndrome Foundation or because they were already patients of my study team.

All participants were known to have Barth syndrome prior to study entry, and all had confirmatory genetic testing showing a pathogenic mutation in the TAZ gene.

By binding to cardiolipin in the inner mitochondrial membrane, elamipretide is believed to stabilize cristae architecture and electron transport chain structure during oxidative stress. I thought it would be great if this could help to stabilize the abnormal cardiolipin components on the inner mitochondrial membrane in Barth syndrome.

We observed improvements in several areas across the study population in the open-label extension part of the study. This includes a significant improvement in exercise performance (as measured by the 6-minute walk test, with an average improvement of 95.9 meters at 36 weeks) and a significant improvement in muscle strength. We also observed a potential improvement in cardiac stroke volume. Most of the adverse events were local injection-site reactions and were mild to moderate in nature.

The TAZPOWER trial has an ongoing open-label extension with the same endpoints as the placebo-controlled portion evaluated on an ongoing basis. In addition, in my laboratory, we are using induced pluripotent stem cells to learn more about how cardiolipin abnormalities affect different cell types in an effort to understand the tissue specificity of disease. This will help us to understand whether different aspects of Barth syndrome would necessitate individual management or clinical monitoring strategies.

Mitochondrial inner membrane dysfunction is increasingly recognized as a major aspect of the pathology of a wide range of mitochondrial conditions. Therefore, based on the role of stabilizing mitochondrial membrane components, elamipretide has a potential role in many disorders of the mitochondria.

Yes, this is what we would call "secondary mitochondrial dysfunction" (meant to differentiate from "primary mitochondrial disease," which is caused by defects in genes that encode for mitochondrial structure and function). Approaches intended to protect the mitochondria from further damage, such as antioxidants or strategies that can bypass the mitochondria for ATP production, could overlap as treatment for primary mitochondrial disease and secondary mitochondrial dysfunction.

This is something that is much discussed as a newer consideration for families who are affected by disorders of the mitochondrial DNA, but not something I have experience with firsthand.

Yes. The United Mitochondrial Disease Foundation and the Mitochondrial Medicine Society collaborated to develop the Mito Care Network, with 19 sites identified as Mitochondrial Medicine Centers across the US.

Andrew Wilner is an associate professor of neurology at the University of Tennessee Health Science Center in Memphis, a health journalist, and an avid SCUBA diver. His latest book is The Locum Life: A Physician's Guide to Locum Tenens.

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Anemia also known as iron-poor blood is a condition that develops when either the blood doesn't have enough red blood cells or the concentration of hemoglobin in red blood cells is very low. Hemoglobin is the iron-containing protein in red blood cells that carries oxygen from the lungs to the rest of the body. When there are fewer red blood cells than normal or low levels of hemoglobin, the body doesn't get enough oxygen-rich blood for healthy functioning, which is what causes the symptoms of anemia.

Anemia is the most common blood disorder in the United States, affecting nearly 3 million Americans, according to the Centers for Disease Control and Prevention (CDC).

The term anemia is a broad one that represents several hundred different conditions some of them mild and treatable, others that are quite serious, said Dr. Nancy Berliner, chief of hematology at Brigham and Women's Hospital in Boston. There are three reasons that people are anemic, Berliner said: Either their body can't make enough red blood cells, something is destroying the red blood cells faster than their body can make news ones or blood loss (from menstrual periods, colon polyps or a stomach ulcer, for example) is greater than blood cell production.

There are more than 400 different types of anemia, according to the Pacific Heart, Lung & Blood Institute. Here are a few of the more common and better understood types:

Iron-deficiency anemia: The most common form of anemia is caused by low-iron levels in the body. Humans need iron to make hemoglobin, and most of that iron comes from dietary sources. Iron-deficiency anemia can result from a poor diet or from blood loss through menstruation, surgery or internal bleeding.

Pregnancy also increases the body's need for iron because more blood is needed to supply oxygen to the developing fetus, which may quickly drain the body's available iron stores, leading to a deficit. Problems absorbing iron from food because of Crohn's disease or celiac disease can also result in anemia.

Vitamin deficiency anemia: Besides iron, the body also needs two different B-vitamins folate and B12 to make enough red blood cells. Not consuming enough B12 or folate in the diet or an inability to absorb enough of these vitamins can lead to deficient red blood cell production.

Sickle cell anemia or sickle cell disease (SDC): This inherited disease causes red blood cells to become crescent-shaped rather than round. Abnormally shaped red cells can break apart easily and clog small blood vessels, resulting in a shortage of red blood cells and episodes of pain, according to the Mayo Clinic. People become chronically anemic because the sickle-shaped red cells are not pliable and can't get through blood vessels to deliver oxygen, Berliner said.

SDC occurs most often in people from parts of the world where malaria is or was common, according to the CDC; the sickle cell trait may provide protection against severe forms of malaria. In the U.S., SDC affects an estimated 100,000 Americans.

Thalassemia: Thalassemia is an inherited blood disorder that results in lower-than-normal levels of hemoglobin. This type of anemia is caused by genetic mutations in one or more of the genes that control the production of hemoglobin, according to the National Heart, Lung & Blood Institute (NHLBI).

Aplastic anemia: Aplastic anemia is a rare, life-threatening condition that develops when bone marrow stops making enough new blood cells, including red cells, white cells and platelets.

Aplastic anemia may be caused by radiation and chemotherapy treatments, which can damage stem cells in bone marrow that produce blood cells. Some medications, exposure to toxic chemicals like pesticides, viral infections and autoimmune disorders can also affect bone marrow and slow blood cell production.

Hemolytic anemias: This disorder causes red blood cells to be destroyed faster than bone marrow can replace them. Hemolytic anemias may be caused by infections, leaky heart valves, autoimmune disorders or inherited abnormalities in red blood cells, according to the American Society of Hematology.

Anemia of inflammation: Also called anemia of chronic disease, anemia of inflammation commonly occurs in people with chronic conditions that cause inflammation. This includes people with infections, rheumatoid arthritis, inflammatory bowel disease, chronic kidney disease, HIV/AIDS and certain cancers, according to the National Institute of Diabetes and Digestive and Kidney Diseases.

When a person has a disease or infection that causes inflammation, the immune system responds in a way that changes how the body works, resulting in anemia. For example, inflammation suppresses the availability of iron, so the body may not use and store the mineral normally for healthy red blood cell production, Berliner said. Inflammation may also stop the kidneys from producing a hormone that promotes red blood cell production.

The risk for anemia is higher in people with a poor diet, intestinal disorders, chronic diseases and infections. Women who are menstruating or pregnant are also prone to the disorder.

The risk of anemia increases with age, and about 10% to 12% of people over 65 are anemic, Berliner said. But the condition is not a normal part of aging, so the cause should be investigated when it's diagnosed, she said. Older adults may develop anemia from chronic diseases, such as cancer, or iron-deficiency anemia from abnormal bleeding.

According to NHLBI, the following types of people have an increased risk of developing anemia:

Mild forms of anemia may not cause any symptoms. When signs and symptoms of anemia do occur, they may include the following, according to the NHLBI:

The first test used to diagnose anemia is a complete blood count, which measures different parts and features of the blood: It shows the number and average size of red blood cells, as well as the amount of hemoglobin. A lower-than-normal red blood cell count or low levels of hemoglobin indicate anemia is present.

If more testing is needed to determine the type of anemia, a blood sample can be examined under a microscope to check for abnormalities in the size and shape of the red cells, white cells and platelets.

Related: This man's taste buds disappeared because of a blood condition

The treatment of anemia depends on the specific type of anemia, Berliner said, and anemias caused by nutritional deficiencies respond well to changes in diet. People with iron-deficiency anemia may need to take supplemental iron for several months or longer to replenish blood levels of the mineral. Some people, especially pregnant women, may find it hard to take iron because it causes side effects, such as an upset stomach or constipation, Berliner said.

For vitamin-deficiency anemias, treatment with B12 or folate from supplements (or a B12 shot) and foods, can improve levels of these nutrients in the blood, Berliner said.

Serious problems, such as aplastic anemia, which involves bone marrow failure, may be treated with medications and blood transfusions. Severe forms of thalassemia might need frequent blood transfusions.

Treatment for sickle cell anemia may include pain medications, blood transfusions or a bone marrow transplant.

Additional resources:

This article is for informational purposes only, and is not meant to offer medical advice.

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Bone marrow aspiration and trephine biopsy are usually performed on the back of the hipbone, or posterior iliac crest. An aspirate can also be obtained from the sternum (breastbone). For the sternal aspirate, the patient lies on their back, with a pillow under the shoulder to raise the chest. A trephine biopsy should never be performed on the sternum, due to the risk of injury to blood vessels, lungs or the heart.

The need to selectively isolate and concentrate selective cells, such as mononuclear cells, allogeneic cancer cells, T cells and others, is driving the market. Over 30,000 bone marrow transplants occur every year. The explosive growth of stem cells therapies represents the largest growth opportunity for bone marrow processing systems.

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Europe and North America spearheaded the market as of 2016, by contributing over 74.0% to the overall revenue. Majority of stem cell transplants are conducted in Europe, and it is one of the major factors contributing to the lucrative share in the cell harvesting system market.

In 2016, North America dominated the research landscape as more than 54.0% of stem cell clinical trials were conducted in this region. The region also accounts for the second largest number of stem cell transplantation, which is further driving the demand for harvesting in the region.Asia Pacific is anticipated to witness lucrative growth over the forecast period, owing to rising incidence of chronic diseases and increasing demand for stem cell transplantation along with stem cell-based therapy.

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Japan and China are the biggest markets for harvesting systems in Asia Pacific. Emerging countries such as Mexico, South Korea, and South Africa are also expected to report lucrative growth over the forecast period. Growing investment by government bodies on stem cell-based research and increase in aging population can be attributed to the increasing demand for these therapies in these countries.

Major players operating in the global bone marrow processing systems market are ThermoGenesis (Cesca Therapeutics inc.), RegenMed Systems Inc., MK Alliance Inc., Fresenius Kabi AG, Harvest Technologies (Terumo BCT), Arthrex, Inc. and others

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BENGALURU:Blood cancers could be leukaemia (of white blood cells), lymphoma (of Lymph nodes) or myelomas (of bone marrow) besides some other rare types. These are overall less common than breast, lung and prostate cancers, however, form a big subset of curable cancers.Generally, patients present with bleeding or infections and are mistaken for other causes and accidentally diagnosed with one of the above acute haematological/blood cancers. Acute leukaemia is more common in children.

Chronic leukaemia, on the other hand, are often diagnosed during routine health checkups with high blood counts and enlarged spleen. Often, myelomas present with renal dysfunction, low haemoglobin or bone fractures, and are missed during the early stages. While all these are extremely treatable, the key is to diagnose the problem on time.

Lymphomas present as lymph node swelling and form almost 60 per cent of all blood cancers and treated with some combinations of chemotherapies and biologics. Bone marrow transplantation (or stem cell transplantation) has an important role in haematological cancers. Autologous (own stem cells) and allogenic (donor stem cells) transplants are used.

There is 180-degree change in the way we diagnose and treat these set of disorders. High-end molecular diagnostics is basis of typing them enabling precision diagnosis and treatment. Monoclonal antibodies, inhibitors and small molecules (biologic therapies) make the treatment much more effective with lesser side effects.

Newer therapies like CAR-T (Chimeric Antigen Receptor-T) cell therapies are used for relapsed acute lymphoblastic leukaemia, large B cell lymphoma and myeloma. However cost of such therapies at this juncture is prohibitive. But with higher applications and wider utilisation, these genetic modification therapies will be more and more accessible.The author is medical oncologist andhemato-oncologist,Vikram Hospital, Bangalore

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Machines intended to work in the body should probably be made out of cells from your body.

There are two stories I would like to tell with this edition of Business Unusual, the first is about the Darpa funded research to build robots out of living cells, the second is the incredible history of the animal that was used to build the first biological robots - Platannas.

The Defense Advanced Research Projects Agency (DARPA) is an agency of the American Department of Defense. It has funded many projects for military projects that in time have come to be used for civilian applications. The best-known example is the predecessor of the internet.

Why a military agency would fund research into creating living robots might be concerning but the stated objectives include managing environmental clean-ups or improving drug delivery which certainly are worthy pursuits. Of greater concern, are the ethical questions that are raised by creating new forms of a living organism. At the moment the designs dont attempt to make them self-replicating but that is part of the future plans.

Robots typically are designed and programmed to perform a specific task. Until now they would have been constructed out of non-living materials. These robots are also designed for a specific task but created from living cells. The choice of cell and the specific construction determines what action or function the living robot can perform.

One function that was attempted was movement. Starting from scratch researchers used stem cells from a frog to create skin cells and heart cells. The heart cells are muscles and so can contract while heart cells are able to do so rhythmically. Using those properties a machine learning program was tasked with testing thousands of configurations to determine which design would use the least cells to achieve the motion required. Once the best designs were determined, the living robots were constructed by researchers manipulating individual cells under a microscope.

The tiny constructed robots demonstrated that living robots designed by computer could offer an alternative to traditionally constructed machines. Future versions would look to make the constructions more complex and eventually able to self replicate.

One intended function was using a swarm of living robots with the ability to decompose plastic to be used to remove microplastics in the ocean. That may be a long way off, but if it is to become a reality the best time to start working on it is now.

Another application might be to not find plastic in the sea, but cancers in your body. Your body is already very good at doing so, but as we age and at certain times of our lives it becomes more challenging to correctly identify and kill cancer cells when they are still only tiny tumours.

This would require building robots consisting of your own body cells arranged in a way to allow them to move through the body and specifically find the corrupted cells. Adding them in numbers as we age may reduce the chance of developing tumours or even help the body recover after exposure to damaging external factors like sun damage to your skin.

This too is a long way off, but if successful and added to the many other options for extending and improving our lives then the research is most welcome.

_Image credit: Wikipedia African clawed frog_

Setting the other issues relating to building living robots aside, you might wonder why a frog from South Africa was chosen to build the first living robots.

It was not a random choice but points to a fascinating history that makes this particular frog one that has helped humanity overcome medical issues on a number of occasions.

A pregnancy test these days simply requires peeing on a stick. The reaction to a specific hormone in the urine can be isolated in minutes and let you know if you are pregnant within days of it occurring. It was not always this easy, the first method we are aware of would see a potentially pregnant woman urinate on ungerminated wheat and barley and wait a week or so to see if it germinated. Incredibly it works and was first mentioned over 3 000 years ago by the Egyptians. It was scientifically tested in the 1960s and found to be 70% accurate.

There were a variety of other methods used most on the expectation that something in the urine of females could be used to confirm pregnancy. In the 1920s it was injecting urine into female rabbits that after a day would require the examination of the rabbit ovaries. If swollen the woman was pregnant. In order to do the examination the rabbit was always killed and so the search continued for a better option.

Enter Lancelot Hogben, an English researcher lecturing in Cape Town in the early 1930s. He advised a student to consider using the local platanna as a potential for use as a model organism for biological tests. His hunch proved correct with Hillel Shapiro and Harry Zwarenstein creating the test to use the frog to indicate pregnancy.

The frog would be injected and in hours if the woman was pregnant would produce eggs. Not only was it accurate, but it also would not harm the frog which was easy to keep in a lab and would live for over a decade. As a result, the remarkable frog was exported around the globe and provided the answer to the question, am I pregnant, to the largest population explosion in our history. Most baby boomers parents and indeed many baby boomers would have found out if they were pregnant thanks to this strange-footed frog.

Xenopus literally means strange foot, frogs typically dont have claws which is why the African clawed frog got the name and as for Platanna, that may be a reference to the frog being very flat - plat in Afrikaans.

Given its widespread use for pregnancy and acceptance as a good species for embryonic development when researchers attempted to clone an organism, this frog was once again a key in understanding the process. In 1958, Xenopus was cloned not from splitting an embryonic cell which was the original method, but by using the DNA from an adult specialised cell which replaced the original DNA in a frog egg. The method proved successful and paved the way to allow Dolly the sheep to be cloned from an adult sheep cell in 1996.

We owe a huge debt of gratitude to six species that for a variety of reasons have helped us understand biological processes and how best to deal with disease and the efficacy of drugs. There are nematode worms, fruit flies, zebrafish, chickens, mice and the African clawed toad.

These six animals are our real guinea pigs.

Image credit: Xenobot - Tuft University & University of Vermont

This article first appeared on 702 : Biological robots, that is a thing now

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Biological robots, that is a thing now - CapeTalk

Skin Stem Cells Comments Off on Biological robots, that is a thing now – CapeTalk | February 6th, 2020

Hip replacements, severe burns, spinal cord injuries, blast injuries, traumatic brain injuriesthese seemingly disparate traumas can each lead to a painful complication during the healing process called heterotopic ossification. Heterotopic ossification is abnormal bone formation within muscle and soft tissues, an unfortunately common phenomenon that typically occurs weeks after an injury or surgery. Patients with heterotopic ossification experience decreased range of motion, swelling and pain.

Currently, theres no way to prevent it and once its formed, theres no way to reverse it, says Benjamin Levi, M.D., Director of the Burn/Wound/Regeneration Medicine Laboratory and Center for Basic and Translational Research in Michigan Medicines Department of Surgery. And while experts suspected that heterotopic ossification was somehow linked to inflammation, new U-M research explains how this happens on a cellular scaleand suggests a way it can be stopped.

To help explain how the healing process goes awry in heterotopic ossification, the research team, led by Levi, Michael Sorkin, M.D. and Amanda Huber, Ph.D., of the Department of Surgerys section of plastic surgery, took a closer look at the inflammation process in mice. Using tissue from injury sites in mouse models of heterotopic ossification, they used single cell RNA sequencing to characterize the types of cells present. They confirmed that macrophages were among the first responders and might be behind aberrant healing.

Macrophages are white blood cells whose normal job is to find and destroy pathogens. Upon closer examination, the Michigan team found that macrophages are more complex than previously thoughtand dont always do what they are supposed to do.

Macrophages are a heterogenous population, some that are helpful with healing and some that are not, explains Levi. People think of macrophages as binary (M1 vs. M2). Yet weve shown that there are many different macrophage phenotypes or states that are present during abnormal wound healing.

Specifically, during heterotopic ossification formation, the increased presence of macrophages that express TGF-beta leads to an errant signal being sent to bone forming stem cells.

For now, the only way to treat heterotopic ossification is to wait for it to stop growing and cut it out which never completely restores joint function. This new research suggests that there may be a way to treat it at the cellular level. Working with the lab led by Stephen Kunkel, Ph.D. of the Department of Pathology, the team demonstrated that an activating peptide to CD47, p7N3 could alter TGF-beta expressing macrophages, reducing their ability to send signals to bone-forming stem cells that lead to heterotopic ossification.

During abnormal wound healing, we think there is some signal that continues to be present at an injury site even after the injury should have resolved, says Levi. Beyond heterotopic ossification, Levi says the studys findings can likely be translated to other types of abnormal wound healing like muscle fibrosis.

The team hopes to eventually develop translational therapies that target this pathway and further characterize not just the inflammatory cells but the stem cells responsible for the abnormal bone formation.

The paper is published in the journal Nature Communications. Other U-M authors include: Charles Hwang, William Carson IV, Rajarsee Menon, John Li, Kaetlin Vasquez, Chase Pagani, Nicole Patel, Shuli Li, Noelle D. Visser, Yashar Niknafs, Shawn Loder, Melissa Scola, Dylan Nycz, Katherine Gallagher, Laurie K. McCauley, Shailesh Agarwal, and Yuji Mishina.

Paper Cited: Regulation of heterotopic ossification by monocytes in a mouse model of aberrant wound healing, Nature Communications, DOI: 10.1038/s41467-019-14172-4

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Abnormal Bone Formation After Trauma Explained and Reversed in Mice - Michigan Medicine

Spinal Cord Stem Cells Comments Off on Abnormal Bone Formation After Trauma Explained and Reversed in Mice – Michigan Medicine | February 6th, 2020

Stem Cell Therapy Market: Snapshot

Of late, there has been an increasing awareness regarding the therapeutic potential of stem cells for management of diseases which is boosting the growth of the stem cell therapy market. The development of advanced genome based cell analysis techniques, identification of new stem cell lines, increasing investments in research and development as well as infrastructure development for the processing and banking of stem cell are encouraging the growth of the global stem cell therapy market.

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One of the key factors boosting the growth of this market is the limitations of traditional organ transplantation such as the risk of infection, rejection, and immunosuppression risk. Another drawback of conventional organ transplantation is that doctors have to depend on organ donors completely. All these issues can be eliminated, by the application of stem cell therapy. Another factor which is helping the growth in this market is the growing pipeline and development of drugs for emerging applications. Increased research studies aiming to widen the scope of stem cell will also fuel the growth of the market. Scientists are constantly engaged in trying to find out novel methods for creating human stem cells in response to the growing demand for stem cell production to be used for disease management.

It is estimated that the dermatology application will contribute significantly the growth of the global stem cell therapy market. This is because stem cell therapy can help decrease the after effects of general treatments for burns such as infections, scars, and adhesion. The increasing number of patients suffering from diabetes and growing cases of trauma surgery will fuel the adoption of stem cell therapy in the dermatology segment.

Global Stem Cell Therapy Market: Overview

Also called regenerative medicine, stem cell therapy encourages the reparative response of damaged, diseased, or dysfunctional tissue via the use of stem cells and their derivatives. Replacing the practice of organ transplantations, stem cell therapies have eliminated the dependence on availability of donors. Bone marrow transplant is perhaps the most commonly employed stem cell therapy.

Osteoarthritis, cerebral palsy, heart failure, multiple sclerosis and even hearing loss could be treated using stem cell therapies. Doctors have successfully performed stem cell transplants that significantly aid patients fight cancers such as leukemia and other blood-related diseases.

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Global Stem Cell Therapy Market: Key Trends

The key factors influencing the growth of the global stem cell therapy market are increasing funds in the development of new stem lines, the advent of advanced genomic procedures used in stem cell analysis, and greater emphasis on human embryonic stem cells. As the traditional organ transplantations are associated with limitations such as infection, rejection, and immunosuppression along with high reliance on organ donors, the demand for stem cell therapy is likely to soar. The growing deployment of stem cells in the treatment of wounds and damaged skin, scarring, and grafts is another prominent catalyst of the market.

On the contrary, inadequate infrastructural facilities coupled with ethical issues related to embryonic stem cells might impede the growth of the market. However, the ongoing research for the manipulation of stem cells from cord blood cells, bone marrow, and skin for the treatment of ailments including cardiovascular and diabetes will open up new doors for the advancement of the market.

Global Stem Cell Therapy Market: Market Potential

A number of new studies, research projects, and development of novel therapies have come forth in the global market for stem cell therapy. Several of these treatments are in the pipeline, while many others have received approvals by regulatory bodies.

In March 2017, Belgian biotech company TiGenix announced that its cardiac stem cell therapy, AlloCSC-01 has successfully reached its phase I/II with positive results. Subsequently, it has been approved by the U.S. FDA. If this therapy is well- received by the market, nearly 1.9 million AMI patients could be treated through this stem cell therapy.

Another significant development is the granting of a patent to Israel-based Kadimastem Ltd. for its novel stem-cell based technology to be used in the treatment of multiple sclerosis (MS) and other similar conditions of the nervous system. The companys technology used for producing supporting cells in the central nervous system, taken from human stem cells such as myelin-producing cells is also covered in the patent.

Global Stem Cell Therapy Market: Regional Outlook

The global market for stem cell therapy can be segmented into Asia Pacific, North America, Latin America, Europe, and the Middle East and Africa. North America emerged as the leading regional market, triggered by the rising incidence of chronic health conditions and government support. Europe also displays significant growth potential, as the benefits of this therapy are increasingly acknowledged.

Asia Pacific is slated for maximum growth, thanks to the massive patient pool, bulk of investments in stem cell therapy projects, and the increasing recognition of growth opportunities in countries such as China, Japan, and India by the leading market players.

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Global Stem Cell Therapy Market: Competitive Analysis

Several firms are adopting strategies such as mergers and acquisitions, collaborations, and partnerships, apart from product development with a view to attain a strong foothold in the global market for stem cell therapy.

Some of the major companies operating in the global market for stem cell therapy are RTI Surgical, Inc., MEDIPOST Co., Ltd., Osiris Therapeutics, Inc., NuVasive, Inc., Pharmicell Co., Ltd., Anterogen Co., Ltd., JCR Pharmaceuticals Co., Ltd., and Holostem Terapie Avanzate S.r.l.

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Stem Cell Therapy Market Trends and Growth, Outlook, Research, Trends and Forecast to 2025 - Instant Tech News

Cardiac Stem Cells Comments Off on Stem Cell Therapy Market Trends and Growth, Outlook, Research, Trends and Forecast to 2025 – Instant Tech News | February 6th, 2020

Research into alternative stem cell sources has identified urine derived renal progenitor cells (UdRPCs) as a possible option for use in regenerative kidney therapies in the future.

Scientists have demonstrated their protocol for the reproducible isolation of kidney stem cells from human urine. These urine derived renal progenitor cells (UdRPCs) could be used to provide easier access to stem cells for regenerative kidney therapies and modelling diseases for R&D.

A shortage of donor organs and the risks and pain associated with bone marrow stem cell extractions and third trimester amniotic fluid collection have encouraged researchers to find alternative sources of stem cells. According to scientists, several laboratories have indicated urine could be an alternative source, at least for kidney stem cells, so the researchers from Heinrich Heine University-Duesseldorf (HHU) Germany,set out to complete a comprehensive molecular and cellular analysis of these cells.

UdRPCs should be considered as the choice of renal stem cells for facilitating the study of nephrogenesis, nephrotoxicity, disease modelling and drug development

Their study, published in Scientific Reports, revealed that UdRPCs isolated from ten individuals express both markers typically seen in bone marrow-derived mesenchymal stem cells (MSCs) and renal stem cells. The renal stem cell markers, according to the paper, allow UdRPCs to be differentiated into cell types present in the kidney, eg, podocytes and the proximal and distal tubules. The study also showed that these progenitor cells have similar properties to amniotic fluid-derived stem cells (AFCs).

Wasco Wruck, bioinformatician and co-author of the study, said: It is amazing that these valuable cells can be isolated from urine and comparing all the genes expressed in UdRPCs with that derived from kidney biopies we could confirm their renal and renal progenitor cell properties and origin.

According to Martina Bohndorf, a study co-author, UdRPCs can also be easily and efficiently reprogrammed into induced pluripotent stem cells using a non-viral integration-free and safe method.

Dr James Adjaye, study senior author and professor at the Institute for Stem Cell Research and Regenerative Medicine (ISRM) in the medical faculty of HHU, revealed that one of the most promising options in the near future is the use of transplantable renal stem cells (UdRPCs) for treatment of kidney diseases as a complementary option to kidney organs. He concluded that human UdRPCs should be considered as the choice of renal stem cells for facilitating the study of nephrogenesis, nephrotoxicity, disease modelling and drug development.

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Kidney stem cells isolated from urine could be regenerative therapies - Drug Target Review

Bone Marrow Stem Cells Comments Off on Kidney stem cells isolated from urine could be regenerative therapies – Drug Target Review | February 5th, 2020

Mesoblast Tenders Completed Biologics License Application

Mesoblast Limited (MESO) announced that it has filed a completed Biologics License Application (BLA) with the United States Food and Drug Administration for its lead allogeneic cell therapy Ryoncil. The therapy is aimed at treating children with steroid-refractory acute graft versus host disease (SR-aGVHD).

Mesoblast submitted the final module of its rolling BLA submission on January 31, 2020. This module covers various aspects related to manufacturing and quality control. The drug candidate currently has Fast Track designation assigned to it and on the basis of this tag, the company is now seeking the FDA to carry out Priority Review of its BLA.

Subject to the approval of the therapy, the company is looking to launch it in the US markets in 2020. CEO Dr. Silviu Itescu said, "This is a major corporate milestone for Mesoblast." The company is expected to use the insights gained from its Temcell product in Japan for the marketing of Ryoncil.

Acute Graft versus Host disease affects nearly 50 percent of patients given an allogeneic Bone Marrow transplant. It is estimated that nearly 30,000 patients undergo bone marrow transplants worldwide. The mortality rate for patients suffering from actual GVHD is close to 90 percent. Currently, there is no FDA approved treatment for this in the United States for children under 12.

Ryoncil has been tested on 309 children suffering from SR-aGVHD during three different studies. It was employed as salvage therapy on 241 children with SR-aGVHD (80% Grade C/D) who failed institutional standard of care. It has also been tested as first line therapy for an open label Phase 3 trial in 55 children with SR-aGVHD. RYONCIL, is an investigational therapy comprising culture-expanded mesenchymal stem cells. These stem cells are taken from the bone marrow of an unrelated donor. The drug is administered to patients as intravenous infusions.

Mesoblast specializes in developing allogeneic cellular medicines. The company uses its proprietary cell therapy technology platform for research and development purpose. It has strong drug pipeline with products such as Remestemcel-L, Revascor, MPC-06-ID and MPC-300-IV. Revascor and MPC-06-ID have completed patient enrollment for its Phase 3 trials. The former drug candidate is aimed at treating advanced chronic heart failure while the latter is targeted at treating chronic low back pain caused by degenerative disc disease. The companys Temcell and Alofisel drugs are already approved in Japan and Europe, respectively.

Mesoblast has posted strong operative results as well. The company had reported 46 percent growth in its revenue during the first quarter of 2020. Mesoblast ended the quarter with $34.5 million in cash while its pro forma cash in hand stood at $100 million. The company also reported its strategic partnership with Grunenthal, which entitles Mesoblast to receive up to $150 million in upfront and milestone payments. The collaboration will also result in commercialization milestone payments. Such milestone payments have the potential to cross $1 billion mark.

Mesoblast stock has performed strongly in the market. The stock has charted over 200 percent in the past 12 months. Currently, it is trading close to its 52-week high of $10.88 and has potential to maintain its positive trajectory as the company forges ahead with its research and development activities and marketing efforts.

Waters Corporation (WAT) reported its fourth-quarter earnings and provided guidance for 2020. The company registered $716 million in revenue for the fourth quarter, in line with the revenue of $715 million it had reported for the corresponding quarter of the previous year. Its GAAP diluted earnings per share stood at $3.12 per share, up from $2.46 on year-on-year basis.

For the full fiscal year 2019, the companys revenue stood at $2.4 billion, down 1 percent from $2.42 billion in revenue it had earned in fiscal year 2018. The EPS for the fiscal year stood at $8.69, up from $7.65 for the previous year. The non GAAP EPS also increased from $8.29 to $8.99 for fiscal year 2019.

The company reported that its sales in both the pharmaceuticals and industrial market declined by 1 percent. However, its sales into the government and academic market grew 8 percent. Chris OConnell, Chairman and Chief Executive Officer of Waters Corporation, said, We were encouraged by the increasing impact in the fourth quarter of our new products launched during 2019.

While its full-year and fourth-quarter numbers were strong, the company provided rather lackluster guidance for fiscal year 2020. Waters Corporation expects its full-year revenue to increase by 1 percent to 3 percent. Its non GAAP EPS will likely remain between $9.15 and $9.40, lower than consensus estimate of $1.75. For its first quarter, Waters Corporations non GAAP EPS for the first quarter is expected to be in the range of $1.55 and $1.65. The consensus estimate for non GAAP EPS guidance was at $1.75.

EyePoint Pharmaceuticals (EYPT) reported its new exclusive licensing deal with Equinox Science. The deal involves the development of vorolanib for treating wet age-related macular degeneration, retinal vein occlusion and diabetic retinopathy. Vorolanib is a tyrosine kinase inhibitor.

EyePoint elaborated that its drug candidate EYP 1901, which incorporates vorolanib, uses a miniaturized, sustained release and injectable intravitreal drug delivery system offering six months duration. The company has used its bioerodible Durasert technology for this purpose. EyePoint is optimistic about the combination of vorolanib with Durasert technology for delivering superior results.

Under the terms of the agreement, EyePoint will take care of development and global commercialization of the treatment. However, the global commercialization will exclude China, Hong Kong, Taiwan and Macau regions. For this purpose, EyePoint will pay $1 million to Equinox Science as upfront payment. It will also pay development and regulatory milestones and post commercialization royalties.

EyePoint recently concluded a positive Type B pre investigational New Drug meeting with the FDA. The meeting clarified the pathway for a Phase 1 clinical trial. The company expects to present the data from Phase 1 trial during the second half of 2021. Nancy Lurker, President and Chief Executive Officer of EyePoint Pharmaceuticals, said, We are encouraged by the potential of vorolanib, as it demonstrated a promising Phase 1 and Phase 2 efficacy signal in prior human wAMD studies as an oral therapy and in preclinical animal studies as intravitreal EYP-1901.

EyePoint is a biopharma company specializing in developing novel ophthalmic products. The company currently has two products available in the market which are Dexycu and Yutiqu. The former is the first approved intraocular treatment for postoperative inflammation while the latter is a three-year treatment of chronic non-infectious uveitis affecting the posterior segment of the eye.

Thanks for reading. At the Total Pharma Tracker, we do more than follow biotech news. Using our IOMachine, our team of analysts work to be ahead of the curve.

That means that when the catalyst comes that will make or break a stock, weve positioned ourselves for success. And we share that positioning and all the analysis behind it with our members.

Disclosure: I am/we are long MESO. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

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Mesoblast Submits BLA, And Other News: The Good, Bad And Ugly Of Biopharma - Seeking Alpha

Bone Marrow Stem Cells Comments Off on Mesoblast Submits BLA, And Other News: The Good, Bad And Ugly Of Biopharma – Seeking Alpha | February 5th, 2020

'This is the beginning of my new life'

I thought my cancer diagnosis was a death sentence, said Lynnette Williams-Briggs, 60, of Seaford, Delaware, who was diagnosed with advanced B-cell lymphoma in 2018.

Briggs cancer is now in complete remission thanks to successful chimeric antigen receptor CAR-T cell therapy she received in August atChristianaCaresHelen F. Graham Cancer Center & Research InstitutesBone Marrow and Stem Cell Transplant Program.

I can breathe again. This is the beginning of my new life, Williams-Briggs said following the treatment that restored her hope for a second chance at life.

She was the first patient to receive CAR-T cell therapy in Delaware. A second patient was treated in December 2019, and doctors are preparing several more patients for CAR-T cell transplants in coming weeks.

The U.S. Food and Drug Administration has approved CAR-T cell therapy to treat patients like Williams-Briggs with highly resistant, B-cell blood cancers, for whom other available options have failed.

CAR-T cell therapy is only available at select cancer centers with specialized expertise in cellular therapies that are recognized for quality by the Foundation for the Accreditation of Cellular Therapy.

The Graham Cancer Centers Bone Marrow and Stem Cell Transplant Program is the only one in Delaware that is certified to treat adult patients with advanced B-cell lymphomas and children and young adults (to age 25) with acute lymphoblastic leukemia, using an FDA-approved drug.

CAR-T cell therapy is highly personalized medicine that attempts to use the bodys natural defenses to fight against cancer. The transplant team extracts millions of T cells, from the patients bloodstream, using a specialized blood filtration process called leukapheresis. The collected T cells are flash-frozen and sent to a lab for reprogramming, and then later infused back into the patient using a process similar to a blood transfusion.

The therapy is considered a living drug with potential benefits that could last for years.

When we first met Ms. Williams-Briggs, her cancer had progressed rapidly despite a third round of chemotherapy, so we knew we had to move quickly, said Graham Cancer Center Hematologist Peter Abdelmessieh, D.O. He worked closely with the bone marrow/stem cell transplant team and Graham Cancer Center leadership over the course of just eight months to develop the CAR-T cell therapy program.

It was truly a team effort to bring CAR-T cell therapy to our community so quickly, Dr. Abdelmessieh said.

CAR-T cell therapy has been extremely effective for many patients like Williams-Briggs, whose PET scan at 90 days confirmed her remission.

The supercharged T cells Williams-Briggs received were genetically modified in the lab to sprout new surface tools that improve their ability to recognize, latch onto and destroy other cells (including cancer cells) that express a specific antigen called CD19. These reprogrammed cells continue to multiply in the body after treatment, remaining on guard to seek and destroy any new cancers that might develop.

With continued success in increasing numbers of patients, it is conceivable that in the not too distant future, CAR-T cell therapy could become the new standard of care, replacing chemotherapy and stem cell transplants for many cancers, Dr. Abdelmessieh said.

The extended recovery period for CAR-T cell therapy is generally two to three months. After the infusion, patients may spend up to three weeks in the hospital to monitor treatment response and any side effects.

During the first 30 days after leaving the hospital, patients are required to remain close to the treatment center for regular follow-up care.

The ability to offer potentially life-saving CAR-T cell therapy is one more reason our patients need not travel further than the Graham Cancer Center for state-of-the-science cancer treatment, said Nicholas J. Petrelli, M.D., Bank of America medical director of the Helen F. Graham Cancer Center & Research Institute.

The Bone Marrow and Stem Cell Transplant Program is an outstanding example of how well our clinical teams work together to drive innovation in patient care.

Although patients normally do not experience the side effects associated with chemotherapy, such as nausea, vomiting or hair loss, CAR-T cell therapy is not without risks. A common side effect, which Williams-Briggs also experienced, is cytokine release syndrome. This is an inflammatory condition that causes flu-like symptoms that may be mild or severe.

The transplant team responded quickly to manage her symptoms while she received expert care on the Bone Marrow Transplant and Oncology unit at Christiana Hospital.

From the moment I first met with my transplant team, I felt like I was part of one big loving family that extended beyond my own loved ones, Williams-Briggs said.

Dr. Abdelmessieh and my ChristianaCare family gave me hope to keep fighting when I really didnt think I would make it. I would have driven anywhere to get life-saving treatment, but I am thankful that I did not have to. I found my miracle closer to home.

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First CAR-T cell cancer therapy patient in Delaware - Dover Post

Bone Marrow Stem Cells Comments Off on First CAR-T cell cancer therapy patient in Delaware – Dover Post | February 5th, 2020

WARSAW (AFP) Submerged in liquid nitrogen vapour at a temperature of minus 175 degrees Celsius, hundreds of thousands of stem cells from all over Europe bide their time in large steel barrels on the outskirts of Warsaw.

Present in blood drawn from the umbilical cord of a newborn baby, stem cells can help cure serious blood-related illnesses like leukaemia and lymphoma, as well as genetic conditions and immune system deficits.

Polish umbilical cord blood bank PBKM/FamiCord became the industrys leader in Europe after Swiss firm Cryo-Save went bankrupt early last year.

It is also the fifth largest in the world, according to its management, after two companies in the United States (US), a Chinese firm and one based in Singapore.

Since the first cord blood transplant was performed in France in 1988, the sector has significantly progressed, fuelling hopes.

Mum-of-two Teresa Przeborowska has firsthand experience.

At five-years-old, her son Michal was diagnosed with lymphoblastic leukaemia and needed a bone marrow transplant, the entrepreneur from northern Poland said.

The most compatible donor was his younger sister, Magdalena.

When she was born, her parents had a bag of her cord blood stored at PBKM.

More than three years later, doctors injected his sisters stem cells into Michals bloodstream. It was not quite enough for Michals needs but nicely supplemented harvested bone marrow.

As a result, Michal, who is nine, is now flourishing, both intellectually and physically, his mum told AFP.

A cord blood transplant has become an alternative to a bone marrow transplant when there is no donor available, with a lower risk of complications.

Stem cells taken from umbilical cord blood are like those taken from bone marrow, capable of producing all blood cells: red cells, platelets and immune system cells.

When used, stem cells are first concentrated, then injected into the patient. Once transfused, they produce new cells of every kind.

At the PBKM laboratory, each container holds up to 10,000 blood bags. Safe and secure, they wait to be used in the future, its Head Krzysztof Machaj, said.

The bank holds around 440,000 samples, not including those from Cryo-Save, he said.

If the need arises, the blood will be ready to use without the whole process of looking for a compatible donor and running blood tests, the biologist told AFP.

For families who have paid an initial nearly EUR600 (USD675) and then an annual EUR120 euros to have the blood taken from their newborns umbilical cords preserved for around 20 years, it is a kind of health insurance promising faster and more effective treatment if illness strikes.

But researchers also warn against unrealistic expectations.

Bone marrow pioneer in Poland Haematologist Wieslaw Jedrzejczak describes promoters of the treatment as sellers of hope, who make promises that are either impossible to realise in the near future or downright impossible to realise at all for biological reasons.

He compares them to makers of beauty products who swear their cream will rejuvenate the client by 20 years.

Various researches is being done on the possibility of using the stem cells to treat other diseases, notably nervous disorders. But the EuroStemCell scientist network warns that the research is not yet conclusive.

There is a list of almost 80 diseases for which stem cells could prove beneficial, US Haematologist Roger Mrowiec, who heads the clinical laboratory of the cord blood programme Vitalant in New Jersey, told AFP.

But given the present state of medicine, they are effective only for around a dozen of them, like leukaemia or cerebral palsy, he said.

Its not true, as its written sometimes, that we can already use them to fight Parkinsons disease or Alzheimers disease or diabetes.

EuroStemCell also cautions against private blood banks that advertise services to parents suggesting they should pay to freeze their childs cord blood in case its needed later in life.

Studies show it is highly unlikely that the cord blood will ever be used for their child, the network said.

It also pointed out that there could be a risk of the childs cells not being useable anyway without reintroducing the same illness.

Some countries, such as Belgium and France, are cautious and ban the storage of cord blood for private purposes. Most European Union (EU) countries however permit it while imposing strict controls.

In the early 2000s, Swiss company Cryo-Save enjoyed rapid growth.

Greeks, Hungarians, Italians, Spaniards and Swiss stored blood from their newborns with the company for 20 years on payment of UER2,500 euros upfront.

When the firm was forced to close in early 2019, clients were left wondering where their stem cells would end up.

Under a kind of back-up agreement, the samples of some 250,000 European families were transferred for storage at PBKM.

The Polish firm, founded in 2002 with PLN2million (around EUR450,000, USD525,000), has also grown quickly.

Present under the FamiCord brand in several countries, PBKM has some 35 per cent of the European market, excluding Cryo-Save assets.

Over the last 15 months, outside investors have contributed EUR63 million to the firm, PBKMs Chief Executive Jakub Baran told AFP.

But the company has not escaped controversy: the Polityka weekly recently published a critical investigative report on several private clinics that offer what was described as expensive treatment involving stem cells held by PBKM.

Read more:
Europe's guardian of stem cells and hopes, real and unrealistic - Borneo Bulletin Online

Bone Marrow Stem Cells Comments Off on Europe’s guardian of stem cells and hopes, real and unrealistic – Borneo Bulletin Online | February 5th, 2020

Spurred by promising clinical results in an important trial, each of the three major CRISPR stocks had a great performance in the second half of 2019. Unfortunately, they didn't keep the momentum going in the first month of 2020.

Shares of Intellia Therapeutics (NASDAQ:NTLA) fell 18.8% in January, according to data provided by S&P Global Market Intelligence. That was followed by a 14.7% loss for shares of CRISPR Therapeutics (NASDAQ:CRSP) and a 10.7% tumble for shares of Editas Medicine (NASDAQ:EDIT).

While each has recovered some ground in the first week of February, this trio of pharma stocks is no stranger to volatility. Investors should probably expect that to continue as clinical programs advance in 2020.

Image source: Getty Images.

In November, CRISPR Therapeutics reported data for the first two individuals in the trial, one with sickle cell disease (SCD) and one with transfusion-dependent beta thalassemia (TDT), treated with its lead drug candidate CTX001. Both enjoyed significant benefits in their standard of living, which investors interpreted as a sign that CRISPR gene editing might actually live up to the hype.

That fueled annual gains of 113% for CRISPR Therapeutics last year. While Editas Medicine and Intellia Therapeutics gained only 30% and 7%, respectively, each had been sitting at a year-to-date loss in October.

What relevance does that have for the tumbles taken in January? First, it's not unusual for stocks to regress to the mean. Stocks that are red hot eventually cool off, while those that tumble without good reason eventually recover some ground.

Second, and the more important consideration for investors, is that the early stage results for CTX001 mean relatively little for the industry's pipeline of CRISPR-based gene editing drug candidates.

Consider that CTX001 is an ex vivo tool. Researchers harvest bone marrow from patients, extract specific types of stem cells, and engineer those with CTX001. The engineered stem cells are then grown in the lab before being reinjected into the patient.

Many other CRISPR-based drug candidates are designed as in vivo tools. That means the gene editing payloads are designed to engineer a patient's DNA while inside the body. An in vivo approach is inherently more complex and will be more difficult to control compared to an ex vivo approach.

Put another way, investors cannot take the promising, early stage results from CTX001 and extrapolate it broadly across all first-generation CRISPR tools. Wall Street certainly isn't, if the correlation between technical approach and stock performance is any guide.

Consider that the two most advanced drug candidates from CRISPR Therapeutics rely on ex vivo engineering. By contrast, the lead drug candidate from Editas Medicine relies on in vivo methods.

The lead pipeline asset from Intellia Therapeutics is also an in vivo tool, though unlike the lead assets from its peers, it has yet to advance to clinical trials.

Investors should expect 2020 to be a busy year for these CRISPR stocks. CRISPR Therapeutics will have more clinical data from CTX001 and the first set of data for its lead oncology asset CTX110.

Similarly, Editas Medicine should have results for EDIT101 and progress additional assets, while Intellia Therapeutics is preparing to finally enter the clinic with NTLA-2001 in the second half of the year.

Investors cannot know if the next batch of results will be as rosy as the initial data for CTX001, but they can probably expect another year of volatile stock movements.

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Here's Why CRISPR Stocks Fell in January - The Motley Fool

Bone Marrow Stem Cells Comments Off on Here’s Why CRISPR Stocks Fell in January – The Motley Fool | February 5th, 2020

"Grand View Research, Inc. - Market Research And Consulting."

According to report published by Grand View Research, the global cell harvesting systems market size was valued USD 3.17 billion in 2016 and is expected to grow at a CAGR of 13.9% over the forecast period.

The globalCell Harvesting System Marketis expected to reach USD 10.17 billion by 2025, according to a new report by Grand View Research, Inc. The increasing demand of stem cellbased therapies, owing to the growing base of aging population and increasing prevalence of chronic diseases, is one of the major factors contributing toward lucrative market growth.

Growing investment on stem cell research is one of the high impact rendering drivers contributing to the demand of stem cells, which thereby contributes to growth of cell harvesting system market. There has been a significant rise in stem cell transplantation rate globally, which is another major driver for increasing demand across the globe. Growth in autologous stem cell transplantation along with increasing stem cell banking is stimulating demand of cell harvesting system.

The potential use of stem cells in regenerative medicine, such as in case of cancer, trauma, congenital diseases, etc., is also one of the factors contributing to the demand for stem cells for research, thereby contributing toward growth of cell harvesting system market across the globe. The rising prevalence of certain diseases such as cancer is expected to drive the growth of this market over the forecast period.

Request a Sample Copy of the Global Cell Harvesting System Market Research Report@ https://www.grandviewresearch.com/industry-analysis/cell-harvesting-systems-market/request/rs1

Further Key Findings From the Report:

Have Any Query? Ask Our Experts@ https://www.grandviewresearch.com/inquiry/3739/ibb

Grand View Research has segmented the global cell harvesting system market on the basis of product, application, end use, and region:

Cell Harvesting System Application Outlook (Revenue, USD Million, 2014 - 2025)

Cell Harvesting System End-use Outlook (Revenue, USD Million, 2014 - 2025)

Cell Harvesting System Regional Outlook (Revenue, USD Million, 2014 - 2025)

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Cell Sorting Market: https://www.grandviewresearch.com/industry-analysis/cell-sorting-market

Cell Therapy Market: https://www.grandviewresearch.com/industry-analysis/cell-therapy-market

About Grand View Research

Grand View Research provides syndicated as well as customized research reports and consulting services on 46 industries across 25 major countries worldwide. This U.S.-based market research and consulting company is registered in California and headquartered in San Francisco. Comprising over 425 analysts and consultants, the company adds 1200+ market research reports to its extensive database each year. Supported by an interactive market intelligence platform, the team at Grand View Research guides Fortune 500 companies and prominent academic institutes in comprehending the global and regional business environment and carefully identifying future opportunities.

Media ContactCompany Name: Grand View Research, Inc.Contact Person: Sherry James, Corporate Sales Specialist - U.S.A.Email: Send EmailPhone: 1-415-349-0058, Toll Free: 1-888-202-9519Address:201, Spear Street, 1100 City: San FranciscoState: CaliforniaCountry: United StatesWebsite: https://www.grandviewresearch.com/industry-analysis/cell-harvesting-systems-market

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Cell Harvesting System Market Size is Estimated to Attain $10.17 Billion By 2025: Grand View Research, Inc - Press Release - Digital Journal

Bone Marrow Stem Cells Comments Off on Cell Harvesting System Market Size is Estimated to Attain $10.17 Billion By 2025: Grand View Research, Inc – Press Release – Digital Journal | February 5th, 2020

Cancer | One of the most common disease in the world

Cancer is the second leading cause of death globally which has caused over nine million deaths in 2018. As per the World Health Organization (WHO), one in 5 men and one in 6 women worldwide develop cancer during their lifetime, and one in 8 men and one in 11 women die from the disease.

But recently the first science minister of Colombia claimed that she has created a fungus extract drink which can treat cancer. After this unproven claim became public, it caused massive chaos which led to the resignation appeal to the minister.

Unproven claims by Mabel Gisela Torres

It was in 2019 December when Colombian President Ivn Duque Mrquez appointed molecular biologist Mabel Gisela Torres to be the first head of the newly created Ministry of Science, Technology and Innovation. Only a few nations knew who she was and Gustavo Quintero Hernndez, the dean of the School of Medicine and Health Sciences at Del Rosario University mentioned her as a "total stranger," after she took over the newly formed ministry.

But at this current moment, she is one of the well-known and most debated person as Torres, who is an expert in fungi from the Technological University of El Choc in Quibd who used an extract from a member of the Ganoderma family of mushrooms to create a tea-like drink to treat 40 people with cancer.

It should be mentioned that the Colombian minister had published 21 scientific articles, largely on a type of mushroom used in traditional Chinese medicine and claimed to have created cancer remedy. But claiming that she found a cancer curing fungus extract made her receive calls to resign. She claimed that already 40 patients took the medicine and some of them went into remission after consuming the potion.

Controversy over cancer treatment

After making such claims, the scientists asked her why she did not follow the widely considered steps to develop the medication. It was also revealed that her finding was not published in any peer-reviewed scientific journal. She neither offered a clinical trial for this cancer remedy nor consulted with an ethics committee, which caused fear that it was an unproven treatment method and that she might be putting the lives of her patients in danger.

But in an interview with Colombia's El Espectador newspaper, Torres defended treatment and said that some traditional treatments have a scientific basis, but the knowledge is not presented in the standard way. In addition, she mentioned that Ganoderma had previously passed toxicity tests in Asia more than 2,000 years ago.

As per Torres, she was looking for potential treatment and a male patient who took the potion was cancer-free after three months. But again, she could not provide any evidence to back her claims. She also compared the treatment with something as safe as having "mango juice at home."

Cancer treatment by Torres

During the interview, she was asked why did she give the patients medically unproven cancer treatment despite not carrying out pre-clinical or clinical studies, or publishing her findings. In response, she mentioned, "I wanted to do an act of rebellion and that is to say: I have the possibility to help people."

However, as per the new report by Nature, Torres would release her data, while the government confirmed that Torres would stay in office.

She said, "At no time have I simplistically proposed that this species [could] be the cure for cancer. I haven't offered a drug, let alone market it. I have rigorously observed the established ethical protocols for scientific experimentation in general and those that apply specifically in my disciplinary field."

Cancer treatment

The usual cancer treatment options include:

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Claims of Colombia science minister to cure cancer with her innovative fungus drink leave scientists shell-shocked - International Business Times,...

Bone Marrow Stem Cells Comments Off on Claims of Colombia science minister to cure cancer with her innovative fungus drink leave scientists shell-shocked – International Business Times,… | February 5th, 2020

NEW YORK, Feb. 5, 2020 /PRNewswire/ --Actinium Pharmaceuticals, Inc.(NYSE AMERICAN: ATNM)("Actinium") today announced that Sandesh Seth, Actinium's Chairman & CEO, will be presenting at the 22nd Annual BIO CEO & Investor Conference. Hosted by the Biotechnology Innovation Organization (BIO), the 22nd Annual BIO CEO & Investor Conference will take place February 10th and 11th at the New York Marriott Marquis in New York City.

Presentation Details

Date:Tuesday, February 11Time:10:15 am ETPresenter:Sandesh Seth, Chairman and CEOLocation:New York Marriott Marquis, Ziegfeld Room

Members of Actinium's Executive team will be available for one-on-one meetings with conference attendees. Those interested in scheduling a meeting with Actinium may do so by contacting Steve O'Loughlin, Principal Financial Officer via email at soloughlin@actiniumpharma.com.

About Actinium Pharmaceuticals, Inc. (NYSE: ATNM)Actinium Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company developing ARCs or Antibody Radiation-Conjugates, which combine the targeting ability of antibodies with the cell killing ability of radiation. Actinium's lead application for our ARCs is targeted conditioning, which is intended to selectively deplete a patient's disease or cancer cells and certain immune cells prior to a BMT or Bone Marrow Transplant, Gene Therapy or Adoptive Cell Therapy (ACT) such as CAR-T to enable engraftment of these transplanted cells with minimal toxicities. With our ARC approach, we seek to improve patient outcomes and access to these potentially curative treatments by eliminating or reducing the non-targeted chemotherapy that is used for conditioning in standard practice currently. Our lead product candidate, apamistamab-I-131 (Iomab-B) is being studied in the ongoing pivotal Phase 3Study ofIomab-B inElderlyRelapsed orRefractoryAcute Myeloid Leukemia (SIERRA) trial for BMT conditioning. The SIERRA trial is over fifty percent enrolled and promising single-agent, feasibility and safety data has been highlighted at ASH, TCT, ASCO and SOHO annual meetings. Apatmistamamb-I-131 will also be studied as a targeted conditioning agent in a Phase 1/2 anti-HIV stem cell gene therapy with UC Davis and is expected to be studied with a CAR-T therapy in 2020. In addition, we are developing a multi-disease, multi-target pipeline of clinical-stage ARCs targeting the antigens CD45 and CD33 for targeted conditioning and as a therapeutic either in combination with other therapeutic modalities or as a single agent for patients with a broad range of hematologic malignancies including acute myeloid leukemia, myelodysplastic syndrome and multiple myeloma. Ongoing combination trials include our CD33 alpha ARC, Actimab-A, in combination with the salvage chemotherapy CLAG-M and the Bcl-2 targeted therapy venetoclax. Underpinning our clinical programs is our proprietary AWE (Antibody Warhead Enabling) technology platform. This is where our intellectual property portfolio of over 100 patents, know-how, collective research and expertise in the field are being leveraged to construct and study novel ARCs and ARC combinations to bolster our pipeline for strategic purposes. Our AWE technology platform is currently being utilized in a collaborative research partnership with Astellas Pharma, Inc.

More information is available at http://www.actiniumpharma.com, http://www.sierratrial.com and our Twitter feed @ActiniumPharma, http://www.twitter.com/actiniumpharma.

Forward-Looking Statements for Actinium Pharmaceuticals, Inc.

This press release may contain projections or other "forward-looking statements" within the meaning of the "safe-harbor" provisions of the private securities litigation reform act of 1995 regarding future events or the future financial performance of the Company which the Company undertakes no obligation to update. These statements are based on management's current expectations and are subject to risks and uncertainties that may cause actual results to differ materially from the anticipated or estimated future results, including the risks and uncertainties associated with preliminary study results varying from final results, estimates of potential markets for drugs under development, clinical trials, actions by the FDA and other governmental agencies, regulatory clearances, responses to regulatory matters, the market demand for and acceptance of Actinium's products and services, performance of clinical research organizations and other risks detailed from time to time in Actinium's filings with the Securities and Exchange Commission (the "SEC"), including without limitation its most recent annual report on form 10-K, subsequent quarterly reports on Forms 10-Q and Forms 8-K, each as amended and supplemented from time to time.

Contacts:

Investors:Hans VitzthumLifeSci Advisors, LLCHans@LifeSciAdvisors.com(617) 535-7743

Media:Alisa Steinberg, Director, IR & Corp Commsasteinberg@actiniumpharma.com(646) 237-4087

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SOURCE Actinium Pharmaceuticals, Inc.

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Actinium Pharmaceuticals, Inc. to Present at the 22nd Annual BIO CEO & Investor Conference - BioSpace

Bone Marrow Stem Cells Comments Off on Actinium Pharmaceuticals, Inc. to Present at the 22nd Annual BIO CEO & Investor Conference – BioSpace | February 5th, 2020

Background

Today's biologic quarry is the hair follicle, depicted on the left. While we all take hair for granted (perhaps the lyric "you don't know what you got till it's gone" is applicable), it is a complex structure lying within the skin. Stem cells are responsible for its growth and coloration, more about them shortly, and the milieu of hormones, as well as cell mediators, controls where hair grows along with its texture. In addition to housing a sebaceous gland, hair follicles have muscles, the arrector pili, responsible for raising your hair, as in the phrase "hair-raising scare," which is a real thing.

Hair follicles go through stages of growth (anagen), rest (telogen), loss (catagen and exogen), as well as renewal (kenogen). The bulbous area at the bottom of the follicle contains those previously mentioned stem cells. Hair follicle stem cells (HFSC) derived embryologically from the same layer as our skin produces a new hair follicle. In contrast, melanocyte stem cells (MeSC) derived from the layer that forms our nervous system, provides pigment to color the hair. During anagen, these stem cells are active; otherwise, they just hang out.

The Study

Looking at the pictures of our recent Presidents over two-terms suggests that stress is involved. But how? To find an answer, the researchers made use of black-coated mice, in a series of increasingly focused experiments.

So yes, my children's antics did turn my hair grey, a hair color I have earned, but not directly. It required the assistance of my sympathetic nervous system. And it may explain why some people under stress retain their hair color; they may well have more of the melanocyte stem cells to burn through. It also points towards the belief that our autonomic nervous system, of which the sympathetics are one component, has a role in cell differentiation and tissue maintenance. Perhaps being more chill can adds days to your life as well as less grey in your hair.

[1] I attribute my hair loss, on the other hand, to my wife.

Source: Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells Nature DOI: 10.1038/s41586-020-1935-3

Image of hair follicle courtesy ofHelix84derivative work in Wikimedia

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Why Does Hair Turn Grey? - American Council on Science and Health

Skin Stem Cells Comments Off on Why Does Hair Turn Grey? – American Council on Science and Health | February 5th, 2020

Electron micrograph showing ridges and grooves on MAP hydrogel microbeads caused by developing stem cells.

Courtsey of Daniel Alge

Baby diapers, contact lenses and gelatin dessert. While seemingly unrelated, these items have one thing in common theyre made of highly absorbent substances called hydrogels that have versatile applications. Recently, a type of biodegradable hydrogel, dubbed microporous annealed particle (MAP) hydrogel, has gained much attention for its potential to deliver stem cells for body tissue repair. But it is currently unclear how these jelly-like materials affect the growth of their precious cellular cargo, thereby limiting its use in regenerative medicine.

In a new study published in the November issue of Acta Biomaterialia, researchers at Texas A&M University have shown that MAP hydrogels, programmed to biodegrade at an optimum pace, create a fertile environment for bone stem cells to thrive and proliferate vigorously. They found the space created by the withering of MAP hydrogels creates room for the stem cells to grow, spread and form intricate cellular networks.

Our research now shows that stem cells flourish on degrading MAP hydrogels; they also remodel their local environment to better suit their needs, said Daniel Alge, assistant professor in the Department of Biomedical Engineering. These results have important implications for developing MAP hydrogel-based delivery systems, particularly for regenerative medicine where we want to deliver cells that will replace damaged tissues with new and healthy ones.

MAP hydrogels are a newer breed of injectable hydrogels. These soft materials are interconnected chains of extremely small beads made of polyethylene glycol, a synthetic polymer. Although the microbeads cannot themselves cling to cells, they can be engineered to present cell-binding proteins that can then attach to receptor molecules on the stem cells surface.

Once fastened onto the microbeads, the stem cells use the space between the spheres to grow and transform into specialized cells, like bone or skin cells. And so, when there is an injury, MAP hydrogels can be used to deliver these new cells to help tissues regenerate.

However, the health and behavior of stem cells within the MAP hydrogel environment has never been fully studied.

MAP hydrogels have superior mechanical and biocompatible properties, so in principle, they are a great platform to grow and maintain stem cells, Alge said. But people in the field really dont have a good understanding of how stem cells behave in these materials.

To address this question, the researchers studied the growth, spread and function of bone stem cells in MAP hydrogels. Alge and his team used three samples of MAP hydrogels that differed only in the speed at which they degraded, that is, either slow, fast or not at all.

First, for the stem cells to attach onto the MAP hydrogels, the researchers decorated the MAP hydrogels with a type of cell-binding protein. They then tracked the stem cells as they grew using a high-resolution, fluorescent microscope. The researchers also repeated the same experiment using another cell-binding protein to investigate if cell-binding proteins also affected stem cell development within the hydrogels.

To their surprise, Alges team found that for both types of cell-binding proteins, the MAP hydrogels that degraded the fastest had the largest population of stem cells. Furthermore, the cells were changing the shape of the MAP hydrogel as they spread and claimed more territory.

In the intact MAP hydrogel, we could still see the spherical microbeads and the material was quite undamaged, Alge said. By contrast, the cells were making ridges and grooves in the degrading MAP hydrogels, dynamically remodeling their environment.

The researchers also found that as the stem cells grew, the quantity of bone proteins produced by the growing stem cells depended on which cell-binding protein was initially used in the MAP hydrogel.

Alge noted that the insight gained through their study will greatly inform further research and development in MAP hydrogels for stem-cell therapies.

Although MAP hydrogel degradability profoundly affects the growth of the stem cells, we found that the interplay between the cell-binding proteins and the degradation is also important, he said. As we, as a field, make strides toward developing new MAP hydrogels for tissue engineering, we must look at the effects of both degradability and cell-binding proteins to best utilize these materials for regenerative medicine.

Other contributors to the research include Shangjing Xin from the Department of Biomedical Engineering at Texas A&M and Carl A. Gregory from the Institute for Regenerative Medicine at the Texas A&M Health Science Center.

This research was supported by funds from theNational Institute of Arthritis and Musculoskeletal and Skin Diseasesof the National Institutes of Health.

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Researchers Explore Hydrogels That Are Promising Materials For Delivering Therapeutic Cells - Texas A&M University

Skin Stem Cells Comments Off on Researchers Explore Hydrogels That Are Promising Materials For Delivering Therapeutic Cells – Texas A&M University | February 5th, 2020