Alan Mackay-Sim, the 2017 Australian of the Year, told Tuesday's GE:Decoding Industry conference that too much university medical research languished for want of a different financing model.

Alan Mackay-Sim, the biomedical scientist who is 2017 Australian of the Year, has called for a new model of public-private partnership to fill the void left by major pharmaceutical companies withdrawing from neuroscience research.

Mr Mackay-Sim, a Griffith University researcher who led a team famed for proving the safety of using nasal cells to repair spinal cord damage, told a GE conference on Tuesday that all of the major pharmaceutical companies had closed or scaled back their neuroscience research units this decade because of the expense and risk in proving that drugs worked in the general population.

"Both Pfizer and Eli Lilly had treatments for Alzenheimer's Disease that failed at that finalstage of the [US Food & Drug Administration] approval process, and it had cost them each $US600million to getthere," he said.

With private enterprise less willing to solve complex neurological problems, Mr Mackay-Sim said it fell to "chumps like me" in the publicly-funded research sector.However, a fundamental mismatch between thebusiness model of universities and corporations had to be solved first.

"The problem is that for a university researcher today, the currency is to get your research published, that's how you get the next grant," he told the conference.

"But once it's published, it's no longer novel, it's not patentable and therefore private enterprise has no interest.Uni researchers are in it for the public good but unfortunately none of that good gets to the public without the commercial imperative."

Mr Mackay-Sim said universities could only afford to patent a fraction of the research they produced, and even then it too often languished for a lack of investors able to fund clinical trials. This happened to Mr Mackay-Sim's own 2001 patent for making stem cells from olfactory sheathing cells.

A new model was required which recognised the "value of future costs saved" in medical research and broadened the pool of potential financial backers, he told The Australian Financial Review on the sidelines of the GE conference.

"Our trial to prove that transplanting olfactory sheathing cells into the spinal cord was safe cost us $1 million, a second trial proving it works might costs us $20 million and the third trial to prove it works broadly might be $100 million or more - but we spend $2 billion a year in Australia caring for those with a spinal cord injury, so surely that's a good investment," Mr Mackay-Simsaid.

Insurance companies were a relatively untapped source of funding for medical research, he added, given their commercial interest in reducing the cost of medical care.

Patentable drugs had a hard enough time being commercialised, but it was even more difficult to fund trials for improved procedures.

"A friend of mine [University of WA Professor Sarah Dunlop] is trying to get up a clinical trial where people with spinal cord injuries are cooled as soon as the first responders get there, like what happens with heart attack patients," Mr Mackay-Sim said.

The slowing of the metabolism through cooling is thought to provide an opportunity for interventions that could increase the mobility of someone with a spinal cord injury.

"But it's a process, not a drug, it's not really patentable so it's proving a struggle to get funding despite this maybe meaning the difference between quadraplegiaand just having an arm immobilised."

The potential value of university-generated medical research couldbe recognised and supported by business earlier if a new kind of public-private partnership was supported and incentivised by government, spreading the risks and rewards, according to Mr Mackay-Sim.

"But it will take unis, government, investors, insurers, pharmaceutical companies and perhaps CSIRO coming together, to rethink this system where the patent and guarding all your IP is the model," he said.

Mr Mackay-Sim stressed he was "not a business guy", but said a benefit of being Australian of the Year was the access he was getting to people who could collaborate on a new funding model for medical research.

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Australian of the Year Alan Mackay-Sim calls for medical research funding change - The Australian Financial Review

Spinal Cord Stem Cells Comments Off on Australian of the Year Alan Mackay-Sim calls for medical research funding change – The Australian Financial Review | April 11th, 2017

RANCHO CORDOVA, Calif., April 11, 2017 (GLOBE NEWSWIRE) -- Cesca Therapeutics Inc. (KOOL), a market leader in automated cell processing and point-of-care, autologous cell-based therapies, today announced that Dr. Xiaochun (Chris) Xu, Chairman and Interim Chief Executive Officer and Chairman of Boyalife Group, will present an overview of the Companys cardiovascular clinical research program at the 2017 International Symposium of Translational Medicine in Stem Cell Myocardial Repair, being held April 10-12, 2017 at the Hope Hotel in Shanghai, China.

Details of the presentation are as follows:

Despite recent therapeutic and surgical advances, the effects of peripheral arterial disease, including heart attack and critical limb ischemia (CLI), remain among the worlds leading causes of morbidity and mortality and represent a rapidly escalating public health crisis, noted Dr. Xu. I look forward to presenting a review of our latest findings, including key feasibility study results and an overview of our Phase 3 Critical Limb Ischemia Rapid Stemcell Treatment (CLIRST) trial, which we believe highlight the potential of Cesca Therapeutics proprietary AutoXpress point-of-care platform to deliver autologous cell-based therapies that may represent a new paradigm in patient treatment going forward.

About the Symposium of Translational Medicine in Stem Cell Myocardial Repair

The 2017 International Symposium of Translational Medicine in Stem Cell Myocardial Repair brings together more than 650 of the worlds cardiac disease thought leaders to discuss the potential of translational and regenerative medicine in treating myocardial infarction (MI) and cardiac failure. The symposium is co-sponsored by the Shanghai Society for Cell Biology, the Institute of Health Sciences, the Shanghai Cardiovascular Disease Institute, the Guangzhou Institutes of Biomedicine and Health, and the Key Laboratory of Stem Cell Biology, Shanghai.

About Cesca Therapeutics Inc.

Cesca is engaged in the research, development, and commercialization of cellular therapies and delivery systems for use in regenerative medicine. The Company is a leader in the development and manufacture of automated blood and bone marrow processing systems that enable the separation, processing and preservation of cell and tissue therapeutics. Cesca is an affiliate of the Boyalife Group (http://www.boyalifegroup.com), a China-based industrial-research alliance among top research institutes for stem cell and regenerative medicine.

Forward-Looking Statement

The statements contained herein may include statements of future expectations and other forward-looking statements that are based on managements current views and assumptions and involve known and unknown risks and uncertainties that could cause actual results, performance or events to differ materially from those expressed or implied in such statements. A more complete description of risks that could cause actual events to differ from the outcomes predicted by Cesca Therapeutics' forward-looking statements is set forth under the caption "Risk Factors" in Cesca Therapeutics annual report on Form 10-K and other reports it files with the Securities and Exchange Commission from time to time, and you should consider each of those factors when evaluating the forward-looking statements.

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CESCA Therapeutics to Present at the 2017 International Symposium of Translational Medicine in Stem Cell ... - Yahoo Finance

Cardiac Stem Cells Comments Off on CESCA Therapeutics to Present at the 2017 International Symposium of Translational Medicine in Stem Cell … – Yahoo Finance | April 11th, 2017

First bone marrow stem cell transplantations performed in Armenia

YEREVAN, APRIL 10, ARMENPRESS. The first two stem cell transplantations of bone marrow in Armenia were performed in the Yolyan Hematology Center by Professor Dr. NicolausKrger, head of the transplantation department of Hamburgs Eppendorf Clinic and the Yolyan Hematology Clinics team.

Professor Smbat Daghbashyan, head of the Armenian transplantation doctors team, told reporters the transplantation passed successfully.

The patients, who trusted her health to the doctors, is a woman from Artsakh, who had to travel abroad for undergoing the same surgery. The second patient is a man, who had a repetition of the disease after chemotherapy, he said, adding that 60 patients annually need stem cell transplantation in Armenia.

We will continue cooperation with our colleagues from Hamburg. The patient who had to receive the transplantation in Hamburg, can get it here the same way. We will perform transplantations in 7-10 patients during this year, since this a gradual process, he said.

Dr. NicolausKrger congratulated the Armenian doctors in introducing the new treatment method in Armenia.

This method is considered to be innovative in the world and is used for treating cancerous diseases, he said.

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First bone marrow stem cell transplantations performed in Armenia - Armenpress.am

Bone Marrow Stem Cells Comments Off on First bone marrow stem cell transplantations performed in Armenia – Armenpress.am | April 11th, 2017

Credit: St. Jude Children's Research Hospital

Like private investigators on a stake out, St. Jude Childrens Research Hospital scientists used patience and video surveillance-like tools to identify cells that trigger blood cell development. The findings offer clues for making blood-forming stem cells in the laboratory that may ultimately help improve access to bone marrow transplantation.

The research will likely open new avenues of investigation in stem cell biology and blood development and provide insight to aid efforts to make transplantable hematopoietic stem cells in the lab, said corresponding author Wilson Clements, Ph.D., an assistant member of the St. Jude Department of Hematology.

Blood-forming stem cells are capable of making any type of blood cell in the body. They are also used in transplant therapies for cancers like leukemia or other blood diseases like sickle cell. They are starting to be used to deliver gene therapy. However, a shortage of suitable donors limits access to treatment, and efforts to produce blood from pluripotent stem cells in the laboratory have been unsuccessful. Pluripotent stem cells are the master cells capable of making any cell in the body.

All blood-forming stem cells normally arise before birth from certain endothelial cells found in the interior blood vessel lining of the developing aorta. This processincluding how endothelial cells are set on the path to becoming blood stem cellsis not completely understood.

Clements and first author Erich Damm, Ph.D., a St. Jude postdoctoral fellow, have identified trunk neural crest cells as key orchestrators of the conversion of endothelial cells to blood stem cells. Trunk neural crest cells are made in the developing spinal cord and migrate throughout the embryo. They eventually give rise to a variety of adult cells, including neurons and glial cells in the sympathetic and parasympathetic nervous system, which control feeding, fighting, fleeing and procreating.

Using time-lapse video, the researchers tracked the migration of neural crest cells in the transparent embryos of zebrafish. Zebrafish and humans share nearly identical blood systems, as well as the programming that makes them during development. After about 20 hours, the neural crest cells had reached the developing aorta. After hour 24, the migrating cells had cozied up to the endothelial cells in the aorta, which then turned on genes, such as runx1, indicating their conversion to blood stem cells.

The investigators used a variety of methods to show that disrupting the normal migration of neural crest cells or otherwise blocking their contact with the aorta endothelial cells prevented the birth of blood stem cells. Meanwhile, other aspects of zebrafish development were unaffected.

Researchers have speculated that the endothelial cells that give rise to blood-forming stem cells are surrounded by a support niche of other cells whose identity and origins were unknown, Damm said. Our results support the existence of a niche, and identify trunk neural crest cells as an occupant.

Adult bone marrow includes niches that support normal function and notably feature cells derived from trunk neural crest cells.

The findings also suggest that trunk neural crest cells use a signal or signals to launch blood stem cell production during development. The researchers have eliminated adrenaline and noradrenaline as the signaling molecules, but work continues to identify the signaling proteins or small molecules involved.

The research was supported in part by a grant (R00HL097) from the National Heart, Lung and Blood Institute of the National Institutes of Health; the March of Dimes; and ALSAC, the fundraising arm of St. Jude.

Reference:

Damm, E. W., & Clements, W. K. (2017). Pdgf signalling guides neural crest contribution to the haematopoietic stem cell specification niche. Nature Cell Biology. doi:10.1038/ncb3508

This article has been republished frommaterialsprovided by St. Jude Children's Research Hospital. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Cells Essential for 'Birth' of Blood Stem Cells Revealed - Technology Networks

Bone Marrow Stem Cells Comments Off on Cells Essential for ‘Birth’ of Blood Stem Cells Revealed – Technology Networks | April 11th, 2017

Science Daily

Graphene, electricity used to change stem cells for nerve regrowth ... Science Daily Iowa State University researchers, left to right, Metin Uz, Suprem Das, Surya Mallapragada and Jonathan Claussen are developing technologies to promote ... and more »

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Graphene, electricity used to change stem cells for nerve regrowth ... - Science Daily

Bone Marrow Stem Cells Comments Off on Graphene, electricity used to change stem cells for nerve regrowth … – Science Daily | April 11th, 2017

(NAPSI)You may be surprised to learn that multiple myeloma is the second most common cancer of the blood, after leukemia. It starts in plasma cells, a type of white blood cell. In time, myeloma cells collect in the bone marrow and may damage the solid part of the bone and eventually harm other tissues and organs, such as the skeleton and the kidneys.

In fact, there are approximately 114,000 new cases diagnosed every year. If you or a loved one is among the 230,000 people living with multiple myeloma worldwide there are a few facts you should know.

What Can Be Done

For many people with the disease, an autologous stem cell transplant may be an answer for eligible patients. This involves collecting the patient's own blood-forming stem cells and storing them. He or she is then treated with high doses of chemotherapy or a combination of chemotherapy and radiation. This kills cancer cells but also eliminates the remaining blood-producing stem cells in the bone marrow. Afterward, the collected stem cells are transplanted back into the patient, so the bone marrow can produce new blood cells.

To help people learn more about the disease and its treatments, the Multiple Myeloma Journey Partners Program was created.

This peer-to-peer education program for patients, caregivers and health care providers leverages storytelling as a tool to improve the patient experience. Journey Partners are multiple myeloma patients who have experienced similar emotions, faced the same challenges and asked the same questions about living with the disease. A Multiple Myeloma Journey Partner will come to any community in which 10 or more people would like to attend the free one-hour educational seminar. The main benefit is that multiple myeloma patients know they're not alone, and the program provides educational resources and services that help patients and families navigate their journey to achieve the best possible outcomes.

As John Killip, a Multiple Myeloma Journey Partner, puts it, "It was conversations with my support group, family and health care providers that influenced my decision to have a stem cell transplant in 2008, when I was first diagnosed with multiple myeloma, at the age of 65. Mentoring other multiple myeloma patients is one of the highlights of my life. I became a Journey Partner to share my story and help others with the disease make sense of the diagnosis and overcome the fear of the unknown."

Learn More

For more information or to request a program, you can visit http://www.mmjourneypartners.com. Anyone interested in becoming a Multiple Myeloma Journey Partner can contact the program coordinator listed on the website. The program is sponsored by Sanofi Genzyme, the specialty care global business unit of Sanofi focused on rare diseases, multiple sclerosis, immunology, and oncology.

On the Net:North American Precis Syndicate, Inc.(NAPSI)

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Understanding Multiple Myeloma - Caswell Messenger

Bone Marrow Stem Cells Comments Off on Understanding Multiple Myeloma – Caswell Messenger | April 11th, 2017

Written by AZoNanoApr 11 2017

Iowa State University researchers, left to right, Metin Uz, Suprem Das, Surya Mallapragada and Jonathan Claussen are developing technologies to promote nerve regrowth. The monitor shows mesenchymal stem cells (the white) aligned along graphene circuits (the black). CREDIT: Photo by Christopher Gannon.

Scientists searching for the means to regenerate nerves might find it difficult to acquire the important tools needed for research. One such example is Schwann cells that form sheaths enclosing axons, which are tail-like portions of nerve cells that convey electrical impulses. In addition to promoting regeneration of the axons, the Schwann cells discharge substances, boosting the health of nerve cells.

To put it differently, the Schwann cells prove to be helpful to researchers working towards the regeneration of nerve cells, particularly peripheral nerve cells located outside the spinal cord and brain. However, the count of Schwann cells is too low to be of any use.

Scientists have been using noncontroversial, readily available mesenchymal stem cells that is, bone marrow stromal stem cells with the ability to form cartilage, bone, and fat cells by differentiating them into Schwann cells by means of a chemical process. Unfortunately, this process is costly and laborious.

The Iowa State University research team have been looking for a better way to transform the stem cells into Schwann-like cells, and have created a nanotechnology that employs inkjet printers for printing multi-layer graphene circuits. It also employs lasers to treat and enhance conductivity and the surface structure of the circuits.

The mesenchymal stem cells have been found to adhere and grow in a better manner on the rough, raised, and 3-D nanostructures of the treated circuit. When small doses of electricity of about 100 mV were applied for 10 minutes per day, for a time period of 15 days, the stem cells transformed into Schwann-like cells.

This discovery has made it to the front cover of Advanced Healthcare Materials, a scientific journal. The lead author of the study is Jonathan Claussen, assistant professor of mechanical engineering at Iowa State University and an associate of the U.S. Department of Energys Ames Laboratory. The first authors of the study are Suprem Das, a postdoctoral research associate in mechanical engineering and an associate of the Ames Laboratory, and Metin Uz, a postdoctoral research associate in chemical and biological engineering.

The research has been funded by the Roy J. Carver Charitable Trust, the U.S. Army Medical Research and Materiel Command, and Iowa States College of Engineering, including the Department of Mechanical Engineering. The research has also been supported by The Carol Vohs Johnson Chair in Chemical and Biological Engineering, Surya Mallapragada. She is a co-author of the study, an Anson Marston Distinguished Professor in Engineering, as well as an associate of the Ames Laboratory.

This technology could lead to a better way to differentiate stem cells. There is huge potential here.

Metin Uz

When compared to the standard chemical process with the ability of differentiating only 75% of the stem cells into Schwann-like cells, the highly effective electrical stimulation carried out in the new technique can differentiate 85%. In addition, the electrically differentiated cells generated a nerve growth factor of 80 ng/mm when compared with 55 ng/mm in the case of the chemically treated cells.

The research team believes the outcome might result in changes in the ways nerve injuries are cured inside the body.

These results help pave the way for in vivo peripheral nerve regeneration, where the flexible graphene electrodes could conform to the injury site and provide intimate electrical stimulation for nerve cell regrowth.

The research team

Various benefits of using electrical stimulation for transforming stem cells into Schwann-like cells are reported in the paper:

A graphene inkjet printing process, created in Claussens research lab, is an important part of making the process work. Flexible, inexpensive, and wearable electronics can be produced through the process by making appropriate use of the benefits of wonder-material graphene, namely high stability, high strength, biocompatibility, and higher electrical and heat conductivity.

The research team confronted one major challenge after printing the graphene electronic circuits, the circuits mandated further treatment to enhance the electrical conductivity, normally done using chemicals or high temperatures. Both of these methods can damage the flexible printing surfaces which include paper or plastic films.

Claussen and his colleagues overcame the challenge by developing a computer-controlled laser technology with the ability to selectively irradiate inkjet-printed graphene oxide. This step eliminates ink binders and converts the graphene oxide to graphene by physically connecting millions of tiny graphene flakes together. This improves the electrical conductivity by over a thousand times.

The cooperation between Claussens team of nanoengineers (who developed printed graphene technologies), and Mallapragadas team of chemical engineers (who investigated nerve regeneration), started as a consequence of informal conversations on campus.

This resulted in experimental efforts to grow stem cells on printed graphene and then to perform electrical stimulation experiments.

We knew this would be a really good platform for electrical stimulation. But we didnt know it would differentiate these cells.

Suprem Das

Since the process has been successful in differentiating the stem cells, the scientists believe that there may be further prospective applications to consider. For instance, in future, the technology could be applied to develop absorbable or dissolvable nerve regeneration materials. These could be surgically positioned inside a patients body without the need for subsequent surgery to remove the materials.

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Innovative Process for Differentiating Stem Cells into Schwann-Like Cells - AZoNano

Bone Marrow Stem Cells Comments Off on Innovative Process for Differentiating Stem Cells into Schwann-Like Cells – AZoNano | April 11th, 2017

Pennsylvania state trooper Matt Uram was talking with his wife at a July Fourth party in 2009 when a misjudged spray of gasoline burst through a nearby bonfire and set him alight. Flames covered the entire right side of his body, and after he fell to the ground to smother them, his wife beat his head with her bare hands to put out his burning hair. It was only on the way to the ER, as the shock and adrenaline began to wear off, that the pain set in. It was intense, he says. If you can imagine what pins and needles feel like, then replace those needles with matches.

From the hospital, Uram was transferred to the Mercy Burn Center in Pittsburgh, where doctors removed all of the burned skin and dressed his wounds. It was on the border between a second- and third-degree burn, and he was told to prepare for months of pain and permanent disfigurement. Not long after this assessment, however, a doctor asked Uram if he would be willing to take part in an experimental trial of a new device.

The treatment, developed by German researcher Dr. Jrg Gerlach, was the worlds first to use a patients stem cells to directly heal the skin. If successful, the device would mend Urams wounds using his bodys ability to regenerate fully functioning skin. Uram agreed to the procedure without hesitation.

Five days after the accident, surgeons removed a small section of undamaged skin from Urams right thighabout the size of a postage stampand used it to create a liquid suspension of his stem cells that was sprayed in a fine mist onto the damaged skin. Three days later, when it was time to remove the bandages and re-dress the wounds, his doctor was amazed by what he saw. The burns were almost completely healed, and any risk of infection or scarring was gone.

Pennsylvania State Trooper Matt Uram's arm eventually healed without scarring. RenovaCare

A study subsequently published in the scientific journal Burns described how the spray was able to regrow the skin across the burn by spreading thousands of tiny regenerative islands, rather than forcing the wound to heal from its edge to the inside. The technique meant reducing the healing time and minimizing complications, with aesthetically and functionally satisfying outcomes, the paper stated.

Dozens more burn victims in Germany and the U.S. were successfully treated with the spray following Urams procedure, and in 2014 Gerlach sold the technology to RenovaCare. The medical technology startup has now transformed the proof-of-concept device from a complicated prototype into a user-friendly product called a SkinGun, which it hopes clinicians will be able to use outside of an experimental setting. For that to happen, RenovaCare is preparing clinical studies for later this year, with the aim of Food and Drug Administration approval for the SkinGun.

Once these obstacles are overcome, RenovaCare CEO Thomas Bold believes, the SkinGun can compete with, or even replace, todays standard of care.

Current treatment of severe burns involves transplanting healthy skin from one area of the body and stitching it to another in a process called skin grafting or mesh skin grafting. It is a painful procedure that creates an additional wound at the donor site and can cause restricted joint movement because the transplanted skin is unable to grow with the patient. It is able to cover an area only two to three times as large as the harvested patch. The current standard of care is just horrible, says Bold. We are part of regenerative medicineit is the medicine of the future and will be life-changing for patients.

RenovaCare's SkinGun sprays a liquid suspension of a patient's stem cells onto a burn or wound in order to regrow the skin without scars. RenovaCare

Beyond regulatory matters, there are also limitations to the technology that make it unsuitable for competing with treatments of third-degree burns, which involve damage to muscle and other tissue below the skin. Still, stem cell researcher Sarthak Sinha believes that while the SkinGun may not be that advanced yet, it shows the vast potential of this form of regenerative medicine. What I see as the future of burn treatment is not skin repair but rather functional regeneration of skin and its appendagessuch as hair follicles, glands and fat, says Sinha. This could be achieved by engaging deeper layers of skin and its resident stem cells to partake in tissue regeneration.

Research is already underway at RenovaCare to enable treatment of third-degree burns, which Bold describes as definitely within the range of possibility. Bold claims the adaptations to the SkinGun would allow it to treat other damaged organs using a patients stem cells, but for now the company is focusing solely on burns and wounds to skinthe largest organ of the human body.

Urams burns are now completely unnoticeable. There is no scar tissue or even pigment discoloration, and the regenerated skin even tans. If I show someone where I was burnt, I bet $100,000 they couldnt tell, he says. Theres no scars, no residual pain; its like the burn never happened. Its a miracle.

Uram is frustrated that the treatment is not available to other burn victims, particularly children. I want to see the FDA get off their butts and approve this, he says. A grown man like me to be scarred is OK, but think about the kids that have to live the rest of their lives with pain and scarring. Thats not OK.

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Spray-On Skin: 'Miracle' Stem Cell Treatment Heals Burns Without ... - Newsweek

Skin Stem Cells Comments Off on Spray-On Skin: ‘Miracle’ Stem Cell Treatment Heals Burns Without … – Newsweek | April 11th, 2017

Mouse heart section showing human progenitor cells that formed functional human blood vessels. Purple color signifies human blood vessels, red staining signifies the blood vessels of the mouse that received the human cell implants. Credit: UIC

Researchers from the University of Illinois at Chicago have identified a molecular switch that converts skin cells into cells that make up blood vessels, which could ultimately be used to repair damaged vessels in patients with heart disease or to engineer new vasculature in the lab. The technique, which boosts levels of an enzyme that keeps cells young, may also circumvent the usual aging that cells undergo during the culturing process. Their findings are reported in the journal Circulation.

Scientists have many ways to convert one type of cell into another. One technique involves turning a mature cell into a pluripotent stem cell one that has the ability to become any type of cell and then using chemical cocktails to coax it into maturing into the desired cell type. Other methods reprogram a cell so that it directly assumes a new identity, bypassing the stem-cell state.

In the last few years, scientists have begun to explore another method, a middle way, that can turn back the clock on skin cells so that they lose some of their mature cell identity and become more stem-like.

They dont revert all the way back to a pluripotent stem cell, but instead turn into intermediate progenitor cells, says Dr. Jalees Rehman, associate professor of medicine and pharmacology at UIC, who led the team of researchers. Progenitor cells can be grown in large quantities sufficient for regenerative therapies. And unlike pluripotent stem cells, progenitor cells can only differentiate into a few different cell types. Rehman calls this method to produce new cells partial de-differentiation.

Other groups have used this technique to produce progenitor cells that become blood vessel cells. But until now, researchers had not fully understood how the method worked, Rehman said.

Without understanding the molecular processes, it is difficult for us to control or enhance the process in order to efficiently build new blood vessels, he said.

His group discovered that the progenitors could be converted into blood vessel cells or into red blood cells, depending on the level of a gene transcription factor called SOX17.

The researchers measured the levels of several genes important for blood vessel formation. They saw that as progenitor cells were differentiating into blood vessel cells, levels of the transcription factor SOX17 became elevated.

When they increased levels of SOX17 even more in the progenitor cells, they saw that differentiation into blood vessel cells was enhanced about five-fold. When they suppressed SOX17, the progenitor cells produced fewer endothelial cells and instead generated red blood cells.

It makes a lot of sense that SOX17 is involved because it is abundant in developing embryos when blood vessels are forming, Rehman said.

When the researchers embedded the human progenitor cells into a gel and implanted the gels in mice, the cells organized into functional human blood vessels. Skin cells that had not undergone a conversion did not form blood vessels when similarly implanted.

When they implanted the progenitor cells into mice that had sustained heart damage from a heart attack, the implanted cells formed functional human blood vessels in the mouse hearts and even connected with existing mouse blood vessels to significantly improve heart function.

The human adult skin cells used by Rehmans team can easily be obtained by a simple skin biopsy.

This means that one could generate patient-specific blood vessels or red blood cells for any individual person, Rehman said. Using such personalized cells reduces the risk of rejection, he said, because the implanted blood vessels would have the same genetic makeup as the recipient.

Rehman and his colleagues noticed something else about the progenitor cells they had elevated levels of telomerase the anti-aging enzyme that adds a cap, or telomere, to the ends of chromosomes. As the caps wear away a little bit each time a cell divides, they are believed to contribute to aging in cells, whether in the body or growing in culture in the laboratory.

The increase in telomerase we see in the progenitor cells could be an added benefit of using this partial de-differentiation technique for the production of new blood vessels for patients with cardiac disease, especially for older patients, Rehman said. Their cells may already have shortened telomeres due to their advanced age. The process of converting and expanding these cells in the lab could make them age even further and impair their long-term function. But if the cells have elevated levels of telomerase, the cells are at lower risk of premature aging.

While telomerase has benefits, the enzyme is also found in extremely high levels in cancer cells, where it keeps cell division in overdrive.

We were concerned about the risk of tumor formation, Rehman said, but the researchers didnt observe any in these experiments. But to truly determine the efficacy and safety of these cells for humans, one needs to study them over even longer time periods in larger animals.

Reference:

Zhang, L., Jambusaria, A., Hong, Z., Marsboom, G., Toth, P. T., Herbert, B., . . . Rehman, J. (2017). SOX17 Regulates Conversion of Human Fibroblasts into Endothelial Cells and Erythroblasts via De-Differentiation into CD34 Progenitor Cells. Circulation. doi:10.1161/circulationaha.116.025722

This article has been republished frommaterialsprovided by the University of Illinois at Chicago. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Partial De-differentiation Converts Skin Cells into Blood Vessel Cells ... - Technology Networks

Skin Stem Cells Comments Off on Partial De-differentiation Converts Skin Cells into Blood Vessel Cells … – Technology Networks | April 11th, 2017

As a kid, I was always intrigued with potions and products. My father worked as a scientist, whose specialty was chemistry as well as business. For many years he worked as the Director of Research and Development for the Mennen Company. Perhaps this is where my love of products and researching products began.

Like many women, my skin can be difficult at times. I have eczema which makes it intermittently sensitive, so I have to be careful of the products I use. While researching these products, I also looked into the science supporting them.

As fate would have it while exploring some interesting articles on my Twitter feed recently, I came across an intriguing tweet I just couldnt ignore. It was a tweet by a glamorous NYC dermatologist who was talking about how excited she was to receive her Lifeline Skin Care products in the mail. Her excitement was so infectious; I decided to look into these products for myself, and looking into them, ultimately led me to buy them and to contact the company to see if we could collaborate together, so I could spread the word.

While researching Lifeline Skin Cares products, I also looked into the science supporting them. Lifeline Skin Care products use something I had never heard of before; they use human, non-embryonic stem cells as one of the main ingredients to help tone and reduce the signs of aging.

Science

As a therapist, I not only look for products that work well and that I believe in, but also look at the philosophy of the company. Lifeline Skin Care was a socially conscious company and fit that standard.

Clinical Trials

The original goal for these researchers was to find a cure for diabetes and Parkinsons disease. These scientists created the first non-embryonic human stem cells. This discovery made finding cures for Parkinsons disease and corneal disease more promising. Currently, some of ISCOs most promising research is in the field of Parkinsons disease.

Parkinsons disease (PD) is a long-term degenerative disease of the central nervous system. It mainly affects the motor system and its symptoms usually have a slow-onset. In early stages, the disease is characterized by shaking, slow movement, difficulty in walking, and rigidity. In time, thinking and behavioral problems may occur. Advanced stages of the disease bring dementia.

istock jm1366

International Stem Cell Corporation (ISCO), is the parent company of Lifeline Skin Care and has devoted many years of research to improve this terrible disease. The company has developed a unique method of creating human neural stem cells which when introduced into the brain, promote the recovery of dopaminergic neurons, the brain cells that are originally affected and cause the disease symptoms. ISCOs preclinical studies showed that the administration of these neural stem cells were safe and improved motor symptoms. To date, 3 of the planned total of 12 patients, have entered the clinical trial and have received neural stem cells. At this point in time, all patients have been discharged from their hospital settings and are observed to be meeting clinical expectations.

Lifeline Skin care (LSC) - a subsidiary of ISCO - uses the extracts from human stem cells, (produced by ISCO), and developed for the skin in order to improve the signs of ageing. The latest technology being used to advance a cure for PD is now available for the skin in a line of products produced by LSC. The profits from the sale of these skin care products go directly to ISCO in order to fund the development of a therapy for PD.

From a skincare perspective, not only did Lifeline Skin Cares products feel good on my face, but I started to notice that my skin appeared brighter and less wrinkles, especially around my eyes (love that!).

From a psychological perspective, the younger we look and feel, the more optimistic and hopeful we tend to be about life and future options. I like the idea of feeling young, looking forever fabulous and most of all, being healthy.

Fortunately, Lifeline Skin Care found a way to help women and men look and feel their very best while scientists from their parent company work toward eradicating illness by using their special non-embryonic stem cell technology. Beauty is more than skin-deep; beauty can be on a mission, too.

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Over recent years, I have seen a growing interest in stem cells and a particular preparation called Platelet Rich Plasma (PRP). Many famous athletes including Tiger Woods have received PRP for various musculoskeletal problems and some have credited it with their accelerated healing and more rapid return to play.

PRP is plasma, the liquid part of blood, concentrated with many more platelets than typically found there. Platelets are known for their importance in clotting blood, but they also contain hundreds of proteins called growth factors. These are responsible for the cascade of events naturally involved in tissue repair. Your own innate stem cells are attracted to the site of injury and play a critical role in the healing process.

Typically, PRP is isolated from your own blood, drawn in the office while you wait. The highly concentrated growth factors are then delivered back into the body at the site of interest. PRP injections have been used for musculoskeletal problems such as sprained knees, osteoarthritis, and chronic tendon injuries. Previously, these types of conditions were treated with medications, physical therapy, and surgery, but PRP recipients commonly report less pain and stronger, more stable joints. It may even promote new cartilage formation in aging joints enabling you to put off joint replacement surgery.

PRP can also be very effective in treating chronic tendon injuries, especially tennis elbow, a common injury of the tendons on the outside of the elbow. Previously, cortisone injections were commonly used, but we know steroids will ultimately weaken tendons and promote rupture. In contrast, now PRP treatments lead to stronger tendons.

Promoting healing after tendon surgery is another use for PRP. For example, an athlete with a completely torn heel cord may require surgery to repair the tendon. Healing of the torn tendon can potentially be improved by treating the injured area with PRP during surgery. With a shorter recovery time, less chronic pain and stronger tissue, you can see why athletes love PRP!

More recently, PRP is being used extensively in aesthetic medicine to keep us looking younger and to promote hair growth. In the same ways the growth factors in PRP facilitate tissue repair from injury or surgery, they also regenerate aging skin. PRP injected into the facial skin has been called the vampire facial made famous by some Hollywood stars.

Today we use a more advanced technique called micro-needling. The PRP is layered across your face and delivered to the skin using a handheld device called a Micropen. This device has 12 tiny micro-needles that drive the PRP in, calling in the tissue repair team to get to work! The result is accelerated collagen production with new, thicker, stronger collagen. The procedure is well tolerated and done in the office while you are awake. It takes less than a couple of hours to complete and usually two to three treatments are recommended spaced four to six weeks apart. The collagen repair process can take four to six weeks, we expect to see the full results blossom over the course of months and continue to improve over a year.

The best thing about PRP Micropen Facelift is that theres not serious downtime like you get with laser resurfacing or surgery. Plus, unlike dermal fillers, which will fade in months, these results will continue to improve over the year. Most commonly we treat faces, but the procedure is safe to use all over the body including necks, chests, hands, and even eye lids. It is also quite helpful for minimizing and fading stretch marks.

If you have any questions or want to learn more about PRP for musculoskeletal or skin rejuvenation, please plan to attend our free interactive community lecture on this topic at the Coronado Library Winn Room from 6-7PM on Thursday 04/06/2017!

Lauren Mathewson, ND is Board certified in naturopathic medicine and Patrick Yassini, MD is board certified in family medicine, integrative and holistic medicine. They practice at Peak Health Group, 131 Orange Avenue, #100, Coronado, Calif.; the office number is (619) 522-4005.

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April 10, 2017 06:00 ET | Source: Mesoblast Limited

NEW YORK and MELBOURNE, Australia, April 10, 2017 (GLOBE NEWSWIRE) -- Mesoblast Limited (Nasdaq:MESO) (ASX:MSB) today announced that thePhase 3 trial ofits allogeneic mesenchymal precursor cell (MPC) product candidate MPC-150-IM in patients with moderate to advanced chronic heart failure (CHF)was successful in thepre-specified interim futility analysisof the efficacy endpoint in the trial's first 270 patients. It is expected that the trial will enroll in total approximately 600 patients. After notifying the Company of the interim analysis results, thetrials Independent Data Monitoring Committee (IDMC) additionally stated that they had no safety concerns relating to MPC-150-IM and formally recommended that the trial should continue as planned.

Dr. Emerson C. Perin,Director, Research in Cardiovascular Medicine and Medical Director, Stem Cell Center at the Texas Heart Institute, and a lead investigator on the ongoing Phase 3 trial said: "It is very pleasingto see that thislarge and rigorously conducted Phase 3 trialof Mesoblast's cell therapy was successful in the pre-specified interim futility analysis for the trial's efficacy endpoint in the first 270 patients. Advancedheart failure is a very serious and life-threatening disease, and there is an urgent need to develop a safe and effective new therapy for these patients that may halt or reverse disease progression and prevent the high associated mortality.

Mesoblast Chief Executive Silviu Itescucommented: Passing this interim futility analysis for MPC-150-IM is an important milestone for Mesoblast and our cardiovascular disease program. This validates our strategy and our prioritization of this valuable program.

This ongoing double-blinded randomized (1:1) trial is currently being conducted across multiple study sites in the United States and Canada.It is evaluating MPC-150-IM in adult patients with moderate to advanced New York Heart Association (NYHA) Class II/III chronic heart failure with left ventricular systolic dysfunction. The trials primary efficacy endpoint is a comparison of recurrent non-fatal heart failure-related major adverse cardiac events (HF-MACE) in moderate to advanced CHF patients receiving either MPC-150-IM by catheter injection into the damaged left ventricular heart muscle or sham control. A Joint Frailty Model is the statistical method that evaluates multiplenon-fatal heart failure-relatedevents per patient (such as repeated hospitalizations for decompensated heart failure) while accounting for increased likelihood of a terminal cardiac event (such as death, implantation of a mechanical heart assist device or a heart transplant) for patients with multiple non-fatal heart failure events. In line with best practice for blinded Phase 3 clinical trials, the interim analysis data are only reviewed by the IDMC. Mesoblast, the United States Food and Drug Administration (FDA), and trial investigators are blinded to grouped safety and efficacy data for the ongoing trial as well as the numerical results of this interim analysis.

About Mesoblasts MPC-150-IM Cardiovascular Program MPC-150-IM is Mesoblast's lead allogeneic, cell-based product candidate for the treatment of moderate to advanced chronic heart failure (CHF) due to left ventricular systolic dysfunction.

In Phase 2 results, a single injection of MPC-150-IM into the myocardium of patients with moderate to advanced chronic heart failure prevented any HF related hospitalizations or cardiac deaths over three years of follow-up.1 Nonclinical studies showed that intramyocardial administration of MPCs in animal models of heart failure improved cardiac function and attenuated pathological ventricular remodelling. These effects were attributable, at least in part, to MPC secretion of biomolecules that stimulate reparative processes in the failing heart including new blood vessel formation, cardiac muscle cell survival, and reduction in tissue fibrosis.

MPC-150-IM is also being studied in a Phase 2b trial in 159 patients with NYHA Class IV end-stage heart failure patients in conjunction with implantation of a left ventricular assist device (LVAD).A major objective of this trial, which is being sponsored by the United States National Institutes of Health (NIH), is to assess the ability of MPC-150-IM to help wean patients from a LVAD dependent existence for survival (so-called bridge to recovery).

Additionally, the FDA recently cleared the commencement of a 24-patient trial which is being sponsored by Bostons Childrens Hospital. This study combines Mesoblast's proprietary allogeneic MPC-150-IM product with corrective heart surgery in children under the age of 5 with hypoplastic left heart syndrome.

About Chronic Heart Failure In 2016, more than 15 million patients in the seven major global pharmaceutical markets are estimated to have been diagnosed with CHF.2 Prevalence is expected to grow 46% by 2030 in the United States alone, affecting more than 8 million Americans.3 CHF is a progressive disease and is classified in relation to the severity of the symptoms experienced by the patient. The most commonly used classification system was established by the NYHA and ranges from Class I (mild) to Class IV or end stage (severe). Approximately half of people who develop heart failure die within 5 years of diagnosis.4 Patients with late NYHA Class II or Class III CHF continue to represent a significant unmet medical need despite recent advances in new therapies. CHF causes severe economic, social, and personal costs. In the United States, it is estimated that CHF results in direct costs of $60.2 billion annually when identified as a primary diagnosis and $115 billion as part of a disease milieu.5

1.Perin EC, Borow KM, Silva GV, et al. A phase II dose-escalation study of allogeneic mesenchymal precursor cells in patients with ischemic or nonischemic heart failure. Circ Res. 2015; 117:576-84

2.GlobalData-PharmaPoint (2016): Heart Failure-Global Drug Forecast and Market Analysis to 2025

3.AHA Statistical Update Heart Disease and Stroke Statistics-(2017). Circulation. 2017;131:00-00. DOI: 10.1161/CIR.0000000000000485

4.Mozzafarian D, Benjamin EJ, Go AS, et al. on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics2016 update: a report from the American Heart Association. Circulation. 2016;133:e38-e360

5.A Re-Evaluation of the Costs of Heart Failure and its Implications for Allocation of Health Resources in the United States. Voigt J. Clinl.Cardiol. 37, 5, 312-321 (2014)

About Mesoblast Mesoblast Limited (Nasdaq:MESO) (ASX:MSB)is a global leader in developing innovative cell-based medicines. The Company has leveraged its proprietary technology platform, which is based on specialized cells known as mesenchymal lineage adult stem cells, to establish a broad portfolio of late-stage product candidates. Mesoblasts allogeneic, off-the-shelf cell product candidates target advanced stages of diseases with high, unmet medical needs including cardiovascular conditions, orthopedic disorders, immunologic and inflammatory disorders and oncologic/hematologic conditions.

Forward-Looking Statements This press release includes forward-looking statements that relate to future events or our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to differ materially from any future results, levels of activity, performance or achievements expressed or implied by these forward-looking statements. We make such forward-looking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. Forward-looking statements should not be read as a guarantee of future performance or results, and actual results may differ from the results anticipated in these forward-looking statements, and the differences may be material and adverse. You should read this press release together with our risk factors, in our most recently filed reports with the SEC or on our website. Uncertainties and risks that may cause Mesoblast's actual results, performance or achievements to be materially different from those which may be expressed or implied by such statements, and accordingly, you should not place undue reliance on these forward-looking statements. We do not undertake any obligations to publicly update or revise any forward-looking statements, whether as a result of new information, future developments or otherwise.

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Time-lapse video reveals cells essential for 'birth' of blood stem cells Science Daily The findings offer clues for making blood-forming stem cells in the laboratory that may ultimately help improve access to bone marrow transplantation. "The research will likely open new avenues of investigation in stem cell biology and blood ... and more »

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Newswise Hematologist-oncologist Ahmad Samer Al-Homsi MD, MBA, will lead a new bone marrow transplantation program at NYU Langones Perlmutter Cancer Center for treating blood-borne cancers, including leukemia, lymphoma and multiple myeloma, and potentially utilize transplantation as an adjunct to immunotherapy for solid tumors. He also will investigate ways to reduce graft-versus-host disease (GvHD), in which immune cells in donated blood and marrow attack the tissues of a recipient.

In addition, Al-Homsi will facilitate NYU Langones collaboration with Johns Hopkins School of Medicine to institute haploidentical transplantation at PCC, in which less perfectly matched individuals can serve as donors. The advent of haplo-transplantation at Perlmutter Cancer Center will vastly expand the potential donor pool for patients who require a transplant.

Al-Homsi, who officially joins NYU Langone on June 1, 2017, most recently co-founded the blood and bone marrow transplantation program at Spectrum Health, a major multi-site health system in West Michigan. Prior to joining Spectrum, he was chief of the Division of Hematologic Malignancies & Blood and Marrow Transplantation and director of the stem cell laboratory at Roger Williams Medical Center in Providence, RI, an academic affiliate of Boston University School of Medicine. Al-Homsi also directed the blood and marrow transplantation program and held several clinical and academic posts at the University of Massachusetts and its affiliated medical center.

Al-Homsis research is focused on preventing GvHD, a potentially life-threatening complication of bone marrow transplantation. He has led clinical trials examining innovative combinations of medications to prevent GvHD , including cyclophosphamide and proteasome inhibitors. Such combinations can omit the need for extended and burdensome prophylactic traditional agents and are applicable to patients with limited kidney function who are often denied blood and marrow transplantation.

At Perlmutter Cancer Center, Al-Homsi will work closely with a strong hematology-oncology team that has made important advances in the study and treatment of blood-borne cancers. Patients requiring bone marrow transplantation undergo their treatment at the medical centers Rita J. and Stanley H. Bone Stem Cell/Bone Marrow Transplant Center.

His appointment also complements important programmatic and research efforts underway at NYU Langones Transplant Institute.

Our understanding of hematologic malignancies has advanced greatly over the past decade, to the point that many cases are curable, says Benjamin G. Neel, MD, PhD, director of Perlmutter Cancer Center. Bone marrow transplantation plays a critical role in these advances -- but it doesnt come without risk. Dr. Al-Homsis research holds tremendous promise to curtail negative interactions between host and transplanted cells and make this form of treatment safer and more effective.

About Dr. Al-Homsi

Al-Homsi earned his medical degree from the University of Damascus in his native Syria. He received training in Hematology at the University of Tours in Paris and in Clinical Oncology from the University of Paris VI in France. He then completed his training in the United States, serving an internship and residency in Internal Medicine at Christ Hospital and Medical Center in Oak Lawn, Illinois, and a fellowship in Hematology and Medical Oncology at the University of Massachusetts Medical Center.

His published studies have appeared in Transplantation, Leukemia, Transplant Immunology, Journal of Infectious Diseases, International Journal of Molecular Medicine, Bone Marrow Transplantation, and Biology of Blood and Marrow Transplantation. He also has authored many book chapters and review articles, and has served on editorial boards of several peer-reviewed journals in his medical specialty.

Al-Homsi also is a lead inspector for the Federation for the Accreditation of Cellular Therapy (FACT) and a member of its Clinical Standard Sub-Committee and Outcomes Improvement Committee.

I am delighted to join NYU Langone and its Perlmutter Cancer Center to build a nationally recognized bone marrow transplantation program, Al-Homsi says. We are defeating leukemia, lymphoma and myeloma at increasing rates. At the same time, we must continue to discover ways to ameliorate problems that sometimes come with treatment. I am confident we can make important strides.

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Stem Cell-Sheet Transplantation Possible for Heart Failure Renal and Urology News In the new study, researchers used stem cells from the patient's own thigh muscle to create a patch they placed on the heart. That's in contrast to many past studies, where researchers have injected stem cells often from a patient's bone marrow ... PERSONALIZED CELL THERAPY MARKET GLOBAL INDUSTRY INSIGHTS, TRENDS, OUTLOOK, AND ...satPRnews (press release) all 12 news articles »

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Turning skin cells into blood vessel cells while keeping them young Science Daily Other methods reprogram a cell so that it directly assumes a new identity, bypassing the stem-cell state. In the last few years, scientists have begun to explore another method, a middle way, that can turn back the clock on skin cells so that they lose ...

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Stem cell drug screen yields potential alternative to statins Science Daily Next, they generated induced pluripotent stem cells from these skin cells. Stem cells continually double their numbers while in culture. This meant that a sample of converted skin cells from a single patient with FH provided a renewable source of liver ...

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M

ice that walk straight and fluidly dont usually make scientists exult, but these did: The lab rodents all had a mouse version of Parkinsons disease and only weeks before had barely been able to lurch and shuffle around their cages.

Using a trick from stem-cell science, researchers managed to restore the kind of brain cells whose death causes Parkinsons. And the mice walked almost normally.The same technique turned human brain cells, growing in a lab dish, into the dopamine-producing neurons that are AWOL in Parkinsons, scientists at Swedens Karolinska Institute reportedon Monday in Nature Biotechnology.

Success in lab mice and human cells is many difficult steps away from success in patients. The study nevertheless injected new life into a promising approach to Parkinsons that has suffered setback after setback replacing the dopamine neurons that are lost in the disease, crippling movement and eventually impairing mental function.

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This is not going to happen in five years or possibly even 10, but Im excited about the potential of this kind of cell replacement therapy, said James Beck, chief scientific officer of the Parkinsons Foundation, which was not involved in the study. It could really give life back to someone with Parkinsons disease.

There is no cure for Parkinsons, a neurodegenerative disease that affects an estimated 10 million people worldwide, most prominently actor Michael J. Fox. Drugs that enable the brain to make dopamine help only somewhat, often causing movement abnormalities called dyskinesia as well as bizarre side effects such as a compulsion to gamble; they do nothing to stop the neurodegeneration.

As Parkinsons patients wait, Fox Foundation and scientist feud over drug trial

Rather than replacing the missing dopamine, scientists led by Karolinskas Ernest Arenas tried to replace dopamine neurons but not in the way that researchers have been trying since the late 1980s. In that approach, scientists obtained tissue containing dopamine neurons from first-trimester aborted fetuses and implanted it intopatients brains.Although a 2001clinical trialfound that the transplants partly alleviated the rigidity and tremors of Parkinsons, the procedure caused serious dyskinesia in about 20 percent of patients, Beck said. More problematic is that fetal issue raises ethical concerns and is in short supply.

It was clear that usable fragments of brain tissue were extremely difficult to recover, said Dr. Curt Freed, of the University of Colorado, who pioneered that work.

Instead, several labs have therefore used stem cells to produce dopamine neurons in dishes. Transplanted into the brains of lab rats with Parkinsons, the neurons reduced rigidity, tremor, and other symptoms. Human studies are expected to begin in the US and Japan this year or next, Beck said.

In the Karolinska approach, there is no need to search for donor cells and no cell transplantation or [need for] immunosuppression to prevent rejection, Arenas told STAT. Instead, he and his team exploited one of the most startling recent discoveries in cell biology: that certain molecules can cause one kind of specialized cell, such as a skin cell, to pull a Benjamin Button, aging in reverse until they become like the embryonic cells called stem cells. Those can be induced to morph into any kind of cell heart, skin, muscle, and more in the body.

Muhammad Ali and Parkinsons disease: Was boxing to blame?

Arenas and his team filled harmless lentiviruses with a cocktail of four such molecules. Injected into the brains of mice with Parkinsons-like damage, the viruses infected plentifulbrain cells called astrocytes. (The brains support cells, astrocytes perform jobs like controlling blood flow.)The viruses also infected other kinds of cells, but their payload was designed to work only in astrocytes, and apparently caused no harm to the other cells.

The molecules, called transcription factors, reprogrammed some of the astrocytes to become dopamine neurons, which were first detected three weeks later in the mouse brains. The dopamine neurons were abundant 15 weeks later, an indication that after changing into dopamine neurons the astrocytes stayed changed.

Five weeks after receiving the injections, the mice, which used to have Parkinsons-like gait abnormalities, walked as well as healthy mice. That suggests that direct reprogramming [of brain cells] has the potential to become a novel therapeutic approach for Parkinsons, Arenas told STAT.

That could have value for preserving the brain circuitry destroyed by Parkinsons, said Colorados Freed.

A lot of hurdles need to be overcome before this becomes a Parkinsons treatment. The Trojan horse system for delivering the reprogramming molecules inside viruseswould need to turn more astrocytes into dopamine neurons and leave other kinds of cells alone: Although viruses getting into mouse brain cells apparently caused no harm, that might not be so in people. We will need to use virus with selective [attraction] for astrocytes, Arenas said.

The morphed cells would presumably be ravaged by whatever produced Parkinsons in the first place. But in other cell transplants, Arenas said, the disease catches up with transplanted cells in 15 to 20 years, buying patients a good period of time. He thinks it might be possible to give patients a single injection but hold off some of the reprogramming with a drug, turning it on when the brain again runs short of dopamine neurons.

The basic technology to develop such strategies currently exists, he said.

The Karolinska lab is working to make the techniquesafer and more effective, including by using viruses that would deliver reprogramming molecules only to astrocytes. We are open to collaborations aimed at human studies, Arenas said.

Would patients be willing to undergo brain injections? People with Parkinsons disease, Beck said, are willing to go through a lot for any hope of improvement.

Sharon Begley can be reached at sharon.begley@statnews.com Follow Sharon on Twitter @sxbegle

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Suspended from a tree in the wilds of Tennessee, the remains of his hang-glider entangled in the branches above, his lower left leg pulverised and his chest badly bruised from his dramatic fall into the forest canopy, Alan Mackay-Sim felt hyper-alert from the electricity of adrenalin, the clarity of shock. Only the wind was audible, softly rustling the branches around him as he sucked in the forest air, perfumed with poplar and sweet-gum.

Knowing that the adrenalin coursing through his veins would soon give way to an agonising and possibly debilitating pain, the 28-year-old used these precious minutes to assess his predicament, to figure it out coolly like a man of science.

A broken leg, no doubt shattered in multiple places. Possibly hours before his fellow hang-gliding friends would be able to locate him; if they didn't reach him by nightfall, he could be dangling here until the next morning. Unfastening his harness and climbing down to the ground five metres below was not an option, at least, not without incurring further injury. To prevent blood from pooling and to save his leg, he quickly concluded, he'd have to carefully oh-so carefully free the hang-glider's stirrup bar and one of the ropes from his harness, create a splint for his injured left leg, secure it to his right leg and hoist up both limbs while hanging there like a gammy fruit bat.

Mackay-Sim had only arrived in the US a few weeks before, a post-doctoral researcher from the University of Sydney eager to extend his studies into the olfactory system specifically, what the nose tells the brain at the University of Philadelphia. But on that blustery October day back in 1979, when a freak wind gust whooshing around Lookout Mountain near Chattanooga sent a promising young Australian scientist nosediving into the forest, before a rescue team found himhanging in the tree just before sunset, both legs securely elevated, Mackay-Sim was set to gain some useful insights that would become valuable to him in his later life. Insights that would be peculiarly relevant to his work as a pioneering stem cell researcher specialising in the treatment of spinal cord injuries.

So badly broken was his leg that Mackay-Sim spent more than six months in a wheelchair, and many more months afterwards receiving intensive physiotherapy.

"It gave me some insight into what life's like in a wheelchair, and it stayed with me," says Mackay-Sim, settling into a chair in his office at the Institute for Drug Discovery at Griffith University, just down the corridor from the laboratory where he spent years toiling over petri dishes of nasal stem cells, in his life's mission to treat spinal injuries, hereditary spastic paraplegia and diseases like Parkinson's.

A photo of the late actor Christopher Reeve is pinned on a noticeboard behind him. "I met Christopher in 2003 when he came out for a conference; he was interested in our clinical trials," Mackay-Sim says, looking at the photo. "Then in the following year I spent some time at his home in New York, and we talked a lot about spinal cord injury repair, and his own personal story."

As Mackay-Sim explains, the higher up the spinal cord an injury is, the more severe the effects. "As we know, Christopher fell off a horse and became a full paraplegic on a respirator, but in fact he suffered only a small injury; the problem was that the bleed went straight into his spinal cord. It only takes a very small injury to stop transmission; you can have large injuries to the chest and not suffer long-term repercussions but here, in the neck, a small event can change your life."

Back in the late 1980s, after he started at Griffith University, Mackay-Sim became interested in a set of extraordinary busy-bee cells in the human nose called olfactory ensheathing cells nerve cells that regenerate every single day to recreate our sense of smell. If these wonder cells are continually regenerating, he kept asking himself, could they not be transplanted to another part of the body where cells don't regenerate, like the spinal cord?

Years of scientific slog followed until 2002, when Mackay-Sim was the first researcher in the world to remove cells from the nose of a patient paralysed in a car accident, grow them in a cell culture and then, with the help of surgeons at Brisbane's Princess Alexandra Hospital, implant them in the same patient's spinal cord. "By the time Christopher died in 2006, we'd transferred stem cells from the nose into three patients and shown it was safe to do so," he says. "One of the patients recovered some sensation above the injury, which was hopeful, but one person does not make real scientific evidence."

For Mackay-Sim, the importance of scientific breakthroughs in the treatment of life-threatening illnesses is deeply personal. In 2014, he was diagnosed with multiple myeloma, an incurable form of leukaemia. As a result of the illness, which breaks down bones in an advanced form of osteoporosis, and the punishing series of treatments that followed his diagnosis, involving radiation, chemotherapy and stem cell therapy (albeit a very different form from the one the scientist was researching), Mackay-Sim lost nine centimetres in height and shed more than 15 kilograms of body weight. "I became extremely sick from the chemotherapy just prior to the bone marrow transplant," the 65-year-old recalls. "It was the worst experience of my life."

There was also the initial shock of the diagnosis, and grief for the loss of his health after a highly active life, from football and rowing in his teens to distance cycling, scuba diving and hang-gliding, which he took up while atuniversity. "Both my parents lived into their 80s and 90s and I'd been cycling up to 200 kilometres a week for decades, so I wasn't anticipating something like this."

Still, as a scientist he couldn't help but observe the trajectory of his illness with stricken fascination. "I had some good conversations with my oncologist," he smiles. "As a biologist examining my own biology, it did demystify lots of things. One minute I was a grieving patient, the next an interested scientist."

Above all, Mackay-Sim refuses to sentimentalise his battle with the illness and asks that I don't embroider it in this story by turning it into some kind of triumph of personal will power over disease. "My survival is determined by the vagaries of the particular cancer I've got," he says matter-of-factly. "Some people have nasty genetic diseases that mean they die earlier. For the moment, I feel very healthy."

Surely his extreme fitness at least helped him to survive the ravages of chemo? "I think being fit and active all my life has given me a higher quality of life after treatment," he acknowledges. "But one doctor put it to me that I probably would have sought out treatment earlier if I wasn't so fit, because I dismissed the symptoms as simple back pain from the cycling. It took two years after the chemo and radiation for the pain to go away. 2016 was a year of normality for me my back became stable enough for me to get on a road bike again."

The diagnosis added poignancy to the evening in Canberra in late January when Mackay-Sim, out of 3000- plus nominations, was crowned Australian of the Year. Sitting alongside him were his American-born wife of nearly 34 years, Lisa Peine, a retired primary school teacher, their 28-year-old daughter Matilda, a trainee psychiatrist, and 25-year-old son Callum, an engineer.

Mackay-Sim with wife Lisa Peine in North Queensland in 1983. Photo: Courtesy of Alan Mackay-Sim

Perhaps no Australian of the Year is better placed to recognise just how precious a year can be, and more determined to seize the moment to put science and innovation at the top of the national conversation. A former Queenslander of the Year, Mackay-Sim sees science as vital to our future national wellbeing, especially after the recent wake-up call in international school education rankings, which placed Australia behind Kazakhstan and Slovenia in maths and science.

Mackay-Sim agrees unequivocally with Michelle Simmons, professor of quantum physics at the University of NSW, who drew headlines recently when she declared that the "feminised" nature of Australia's high school physics curriculum (emphasising the sociology of science with essays and theory instead of rigorous lab experiments and mathematical problem-solving) had been an unmitigated failure. Introduced in the 1980s, the approach had resulted in a long, slow decline in standards.

"Scientific understanding comes from learning the processes; it can be hard work but is absolutely essential," Mackay-Sim insists. "The key to a good science education in schools is to get well-trained teachers." (Mackay-Sim has been deeply encouraged by some of the science teachers he's met since winning the award.)

The choice of Mackay-Sim the first scientist honoured as Australian of the Year since immunologist Ian Frazer in 2006 was met with near-universal applause by Australia's scientific community, who no doubt feel dispirited in this post-truth world of climate-change denial, cuts to the CSIRO and the growing view by government agencies that basic research isn't worth it.

"We need to invest in young scientists," Mackay-Sim declared in his acceptance speech, adding that the discovery of new medical treatments can reduce the strain on health budgets. "More than 10,000 Australians live with a spinal cord injury a new person is added to this tally every day." But politicians need to take a long-term view of the benefits of basic research, he tells me, "a view much longer than the political horizon".

The announcement also gave the image of the Australian of the Year awards a much-needed polish. The 2016 winner, Lieutenant-General David Morrison, drew criticism for charging up to $15,000 a pop forpublic speaking engagements, as well as grandstanding about sexism in the military despite his own handling of the army's "Jedi Council" sex scandal, in which demeaning sex videos of women were distributed among a group of soldiers. (It was revealed that Morrison's office knew of the scandal 11 months prior to the former Chief of Army releasing a now-famous condemnation on YouTube of those involved.)

Will Mackay-Sim accept speakers' fees? "I knew nothing about speakers' fees when I accepted the award," he says crisply. "I'm not pursuing money after all, I've spent my life doing public research."

Although he hasn't received any fees to date, Mackay-Sim insists that if they are offered, the funds will be donated to the Hereditary Spastic Paraplegia Research Foundation, his charity of choice.

Mackay-Sim only had a day or so to bask in the glow of being named Australian of the Year before there was a claim his scientific achievements had beenoverstated in the application. A Polish scientist, Professor Pawel Tabakow, after being approached by an Australian journalist in Europe, declared that Mackay-Sim had nothing to do with the world-first surgery using olfactory stem cells that enabled a Polish paraplegic, Darek Fidyka, to walk again. "It is not our business who should be Australian of the Year," Tabakow told The Weekend Australian. "But it is our business when his work is being linked to the surgery of Fidyka. He has no link whatsoever."

The scientific hullaballoo arose from the submission to the Australia Day Council (ADC), which states that Mackay-Sim's research "helped play a central role in proving the safety of science that was a precursor to Dr Tabokow in Poland undertaking the first successful restoration of mobility in a quadriplegic man".

Although Mackay-Sim didn't write the submission to the ADC, doesn't know who did, and never claimed to be involved in Tabokow's work, an artificial straight line was drawn between the two scientists, especially when the word "precursor" was dropped from condensed versions of the ADC's quote in multiple news stories (we'll examine the fallout from the controversy a little later).

Padding amiably about his large, multi-room laboratory, past refrigerator-sized storage cabinets containing cell cultures, past white-coated scientists peering into microscopes, Mackay-Sim seems to be in his element, with every second person saying "Hi", "Hello", or "How are you?" If stem cells are indeedthe microscopic building blocks of the world, this is the tiny universe the scientist feels most comfortable in. But it's a laboratory that now has to hum along without him Mackay-Sim retired late last year, his duties now limited to popping into the university once a week as an emeritus professor.

Later in the day, Professor George D. Mellick, head of Clinical Neurosciences at Griffith, tells me that Mackay-Sim has always set aside time to mentor younger scientists, and to explain sometimes hideously complicated science to a lay audience, but would be the last person to crow about his own scientific achievements.

"One of the things that isn't highlighted very much about Alan's work is his research into Parkinson's. We've been able to learn a lot about Parkinson's by studying cells from people with the disease, and the information coming out of this research will hopefully lead to better treatments."

Back in his office, Mackay-Sim gives me a quick rundown, 101-style, on the human nose. No, the human sense of smell doesn't necessarily decline with age, unless illness or disease set in, and it is astonishingly adept at distinguishing hundreds of thousands of different odours. Yes, women do have a superior sense of smell to men, but the difference is surprisingly only slight. Yes, the first symptom of Parkinson's, before the typical tremors set in, is a reduced sense of smell, as it is with those sufferers who will go on to develop dementia. And yes paws down dogs do have a vastly more powerful sense of smell than humans, although it's impossible to quantify by exactly how much (Mackay-Sim has been known to hide from his spoodle Henry, to measure how long it takes for the dog to find him).

As he relays all this, Mackay-Sim's eyes twinkle and a smile lights up his face: it's easy to see how he'd be the perfect academic for Griffith to call on to schmooze a government minister or potential philanthropist and secure desperately sought-after funding. I ask him about his trademark moustache, which he's had since the early 1990s, when he shaved off a beard. "My wife wouldn't recognise me without it," he jokes. "She says that a small mammal could roost beneath my mouth."

Mackay-Sim, whose double-barrelled surname comes from his paternal grandfather, grew up in middle-class Roseville, on Sydney's leafy North Shore, the third of four brothers. His mother Lois was a nurse during World War II and later a full-time mum while his father Malcolm ran a hardware importing and distributing business, Macsim Distributors (now Macsim Fasteners, owned by Alan's eldest brother, Fraser). At North Sydney Boys' High he was "the opposite of a shit-stirrer. I was vice captain, head of the cadets, played football, was in the rowing team, had a shot at athletics, sang in the choir I did it all."

With wife, Lisa Peine, in Sulawesi, Indonesia, 2007. Photo: Courtesy of Alan Mackay-Sim

After graduating with honours in science from Macquarie University, Mackay-Sim picked up tutoring work in the department of physiology at the University of Sydney, where he completed a PhD on the brain's visual system. Two academic stints in the US followed, first at the University of Pennsylvania from 1979 until 1981, followed by two years at the University of Wyoming, during which time he met his wife Lisa, then living in northern Colorado.

The pair married in 1984, by which time Mackay-Sim had been offered a research role in the department of physiology at the University of Adelaide. He started at Griffith University in 1987, where his research concentrated on the biology of nasal cells.

At the height of the heated moral debate over the use of embryonic stem cells whether the therapeutic potential of stem cells could justify destroying human embryos to extract them Mackay-Sim met Pope Benedict XVI at a Vatican conference in 2005. The Pope congratulated him on his exclusive use of adult stem cells.

"I wasn't avoiding embryonic stem cells for religious reasons," Mackay-Sim explains. "It just so happenedthat I was working with adult stem cells at the time and the conference was looking at alternatives to using embryonic stem cells. But it was a scientific conference and I was impressed with its calibre; the only difference was that men in purple robes were sitting at the back asking questions."

Later in the same trip, Mackay-Sim was invited, along with a host of others, to the Apostolic Palace at Castel Gandolfo the Vatican summer palace. "You feel the history of the Roman Catholic Church, with the Pope coming in with his cardinals and the Swiss Guards," he says. "I'm not a believer, but it was a very powerful experience."

In 2006, the debate over embryonic stem cells virtually vanished when scientist Shinya Yamanaka from Japan's Kyoto University stunned the world by proving that stem cells needn't come from human embryos adult cells can be reprogrammed to act like stem cells, to be returned to an embryo-like state (Yamanaka's discovery won him the Nobel Prize in 2012). "Yamanaka worked out how to genetically engineer any cells so that they had the properties of embryonic stem cells," says Mackay-Sim, who nonetheless continued to focus on adult stem cells only.

Mackay-Sim accomplished his own world first in 2002 when, with the assistance of doctors at Brisbane's Princess Alexandra Hospital, he transplanted olfactory stem cells into the spinal cord of a man crippled in a car accident. The procedure was repeated with two other paraplegic patients at the same hospital and the study wrapped up in 2007.

While the procedures didn't result in any of the patients regaining useful movement in their legs, the results of Mackay-Sim's clinical trials, published in 2005 and 2008, paved the way for further development of olfactory stem cell transplantation.

One researcher who followed Mackay-Sim's trials closely was Geoffrey Raisman from University College London, who visited the Australian team shortly after the first operation in Brisbane to study their work. Raisman later led the British team who worked with Polish surgeon Tabakow on Darek Fidyka in 2012.

Tabakow deployed 100 separate micro-injections of olfactory sheathing cells above and below Fidyka's spinal injury, with the hope these cells would provide a skeleton for nerve fibres to grow and reconnect. A former volunteer firefighter, Fidyka had become paralysed in 2010 after a severe knife attack by the jealous ex-husband of his girlfriend. The repeated stab wounds to Fidyka's back severed his spinal cord, paralysing from the waistdown. (Fidyka's attacker, a fellow firefighter, committed suicide shortly afterwards.)

There's no doubt Tabakow's work was a major advance on Mackay-Sim's research. Tabakow's strategy was to extract ensheathing cells specifically from the olfactory bulbs in Fidyka's nose, grow them in a culture, while also extracting nerve cells from his ankle in a multi-pronged attempt at spinal cord reconstruction. After a series of operations, Fidyka can walk with the assistance of a frame, has regained some bladder control and sexual function, and can ride a tricycle.

Raisman described their new stem cell procedure as "more impressive than man walking on the moon", but it will have be tested on other paraplegics, including those with more severe injuries than Fidyka's, such as car accident victims who have had more of their spinal cord damaged, before it can be declared a reliable method of restoring mobility. As impressive as Tabakow's achievement is, it has still only worked on one patient.

Nobody, however, disputes Mackay-Sim's immense contribution to stem cell transplantation; his work is unimpeachable. If nothing else, he was at the forefront of the science showing that restoring the ability to walk to paraplegics is no longer science fiction. "What I've always said is that we did the first phase of clinicaltrials with olfactory stem cells, and the aim of those trials was to show they were safe," says Mackay-Sim. "That was the first important step."

Mackay-Sim wrote to Tabakow shortly after the controversy blew up, explaining that he didn't write the submission to the Australia Day Council, and was in no way claiming credit for Fidyka's remarkable recovery. "He wrote back a very nice email," says Mackay-Sim. "I believe I've given credit to other scientists in every interview I've given to journalists. I feel comfortable in my behaviour and ethics."

With Prime Minister Turnbull in January this year. Photo: Elesa Kurtz

Mackay-Sim can remember the day when he felt something was wrong terribly wrong. He'd been suffering back pain for months, but dismissed it as old age, or strain from bending over on his bicycle on long rides, and stocked up his pantry with painkillers. "I was in Colorado with Lisa visiting her family, and the pain became so bad I couldn't walk very far. I found the pain eased when I got on my bicycle. I flew home a week before she did; the plane trip back was absolute hell."

What followed was a swift diagnostic journey from his GP to specialists at Brisbane's Wesley Hospital, resulting in a devastating diagnosis. "They suspected something cancerous quite quickly. I didn't realise how ill I was; by this stage, my kidneys weren't coping at all with the antibodies released from my white blood cells, which were going berserk trying to fight the disease. I was at risk of kidney failure and my bones were becoming very fragile. I started therapy almost immediately, in June 2014. Then began the cycles of chemotherapy and stem cell treatment in December."

Since the beginning of last year, however, Mackay-Sim's health has dramatically improved, and even though he's retired to his beachside home in Currimundi on the Sunshine Coast, he is still active in university affairs. He concedes that his health may prevent him from being as active as Rosie Batty, perhaps our most vigorous Australian of the Year to date. But he's already spoken at functions in Brisbane, Sydney and Perth, and will be attending the national March for Science on April 22, which coincides with Earth Day. He moves with the speed and fluidity of a man 10 or 15 years younger.

"I feel very healthy, very energised at the moment," says Mackay-Sim, who is planning a bicycle ride in Italy's Dolomites in July with a couple of mates. (Last year he and his wife went on the Great Victorian Bike Ride, a seven-day ride averaging 85 kilometres a day.)

"I do need to be selective with the number of invitations around Australian of the Year," he concedes, "but I'll do everything I can. After all, what more exciting time could you have to talk about science?"

Original post:
Australian of the Year Alan Mackay-Sim on the advantage of being 'an interested scientist' - The Sydney Morning Herald

Spinal Cord Stem Cells Comments Off on Australian of the Year Alan Mackay-Sim on the advantage of being ‘an interested scientist’ – The Sydney Morning Herald | April 9th, 2017

A team of scientists from the University of California, Los Angeles has been able to synthesize an artificial thymus, a human organ that is important to the bodys immune system. An artificial thymus, they say, could produce necessary cancer-fighting T-cells for the body.

On demand.

T-cells, of course, are white blood cells which naturally fight diseases that develop in or infect the body. These T-cells are artificial, though, so they would have to be engineered to target specific forms of cancer, in order to be effective. Still, if this is manageable, then it could provide scientists and health practitioners with additional natural defensesalbeit, bionicfor attacking disease.

The thymus rests in front of the heart. It uses stem cells from the blood to make immune-boosting T-cells, which literally circulate throughout the body to specifically target things that dont belong. In this case, the thymus would create T-cells that could seek out specific cancerous growths without jeopardizing the health of existing tissue.

For the study, the Japanese researchers looked at 27 patients who had received transplants form stem cells that had been taken from their own thigh muscles. These patients showed no sign of any major complications; most patients also showed significant improvement with their symptoms.

Research team member Gay Crooks comments, We know that the key to creating a consistent and safe supply of cancer-fighting T-cells would be to control the process in a way that deactivates all T-cell receptors in the transplanted cells, except for the cancer-fighting receptors. It is important, of course, to take stem cells from the patient who needs them because the body is likely to reject any foreign stem cells (and their byproducts). Apparently, they have been at this study for more than two decades but, unfortunately, the researchers acknowledge that past attempts only showed modest results. From these results, though, they were able to devise a method for producing sheets of muscle stem cells which could then be attached to the inner layer of the sac (which encloses the heart). These stem cells will stimulate healing through the production of chemicals which encourage cardiac regeneration, though the stem cells, themselves, do not survive in the long term.

The results of this study have been published in the scientific journal Nature Methods.

Read more:
Can An Artificial Thymus, Made from Stem Cells, Pump Out Enough T-Cells To Fight Cancer? - Dispatch Tribunal

Cardiac Stem Cells Comments Off on Can An Artificial Thymus, Made from Stem Cells, Pump Out Enough T-Cells To Fight Cancer? – Dispatch Tribunal | April 9th, 2017