Scientists at The University of Queensland have taken a significant step forward in cardiac disease research by creating a functional beating human heart muscle from stem cells.

Dr James Hudson and Dr Enzo Porrello from the UQ School of Biomedical Sciences collaborated with German researchers to create models of human heart tissue in the laboratory so they can study cardiac biology and diseases in a dish.

The patented technology enables us to now perform experiments on human heart tissue in the lab, Dr Hudson said.

This provides scientists with viable, functioning human heart muscle to work on, to model disease, screen new drugs and investigate heart repair.

The UQCardiac Regeneration Laboratoryco-leaders have also extended this research and shown that the immature tissues have the capacity to regenerate following injury.

In the laboratory we used dry ice to kill part of the tissue while leaving the surrounding muscle healthy and viable, Dr Hudson said.

We found those tissues fully recovered because they were immature and the cells could regenerate in contrast to what happens normally in the adult heart where you get a dead patch.

Our goal is to use this model to potentially find new therapeutic targets to enhance or induce cardiac regeneration in people with heart failure.

Studying regeneration of these damaged, immature cells will enable us to figure out the biochemical events behind this process.

Hopefully we can determine how to replicate this process in adult hearts for cardiovascular patients.

UQ scientists create beating human heart muscle from The University of Queensland on Vimeo.

Each year, about 54,000 Australians suffer a heart attack, with an average of about 23 deaths every day.

The UQ research has been supported by the National Health and Medical Research Council (NHMRC) and the National Heart Foundation.

Heart Foundation Queensland CEO Stephen Vines said the charity was excited to fund such an important research project.

Heart attack survivors who have had permanent damage to their heart tissue are essentially trying to live on half an engine, Mr Vines said.

The research by Dr Hudson and Dr Porello will help unlock the key to regenerating damaged heart tissue, which will have a huge impact on the quality of life for heart attack survivors.

Dr Hudson and Dr Porello are deserved recipients of our highest national research accolade the Future Leader Fellowship Award.

The research is published in Circulation and Development.

Media: Dr James Hudson, j.hudson@uq.edu.au; Kim Lyell, k.lyell@uq.edu.au, 0427 530 647.

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Scientists create 'beating' human heart muscle for cardiac research - UQ News

Cardiac Stem Cells Comments Off on Scientists create ‘beating’ human heart muscle for cardiac research – UQ News | March 16th, 2017

A retina with macular degeneration. (Image: University of Iowa)

An unproven stem cell therapy conducted by a Florida clinic has blinded three patients in an apparent clinical trial gone horribly wrong. The incident showcases the extent to which unscrupulous clinics will take advantage of desperate patientsand how the lack of government oversight contributes to the problem.

As reported in the New England Journal of Medicine, the clinical trialif it can be called thatinvolved three women between the ages of 72 and 88 who were suffering from macular degeneration, a common progressive disease of the retina that leads to loss of vision. The women, all of whom were experiencing various degrees of vision loss, sought the help of a Florida clinic, which claimed to be testing a stem cell procedure designed to treat macular degeneration. Sometime in 2015, a week after stem cells were injected into their eyes, the women became blind. Two years later, doctors say theres virtually no chance the womens vision will be restored.

The authors of the new report, ophthalmologists Jeffrey Goldberg from Stanford University School of Medicine and Thomas Albini from the University of Miami, said the unfortunate incident serves as a call to awareness for patients, physicians and regulatory agencies of the risks of this kind of minimally regulated, patient-funded research.

Stem cells are undifferentiated cells that havent quite decided what they want to be when they grow up. Under the right conditions, these immature cells can be transformed into virtually any kind of cell found in the body, which is why theyve proven useful in regenerative medicine.

Eventually, scientists hope to be able to use stem cells to regenerate damaged tissue and organsand possibly even repair the effects of macular degenerationbut were not there yet. The only truly effective clinical application of stem cells to date has been in bone marrow transplants, in which stem cells extracted from a donors bone marrow are used to produce a fresh blood system for patients suffering from blood disorders such as leukemia. A recent study showed that there are nearly 600 clinics peddling unproven stem-cell procedures in the United States for a wide range of conditions, including arthritis, autism, cerebral palsy, stroke, muscular dystrophy, and cancer.

As noted in the NEJM report, two of the three patients learned about the stem cell trial for macular degeneration on ClinicalTrials.gov, a registry run by the US National Library of Medicine. The listings on this site arent fully scrutinized for scientific efficacy. The patients were reportedly under the assumption that they were participating in a bonafide clinical trial, but the consent form and other materials made no mention of a trial. Tellingly, each patient had to pay $5,000 for the procedure. This is highly unorthodox for a clinical trial, and it should have been cause for alarm. Im not aware of any legitimate research, at least in ophthalmology, that is patient-funded, Albini said in a statement.

The NEJM study didnt identify the Florida clinic responsible, but (conveniently) the authors provided the name of the trial: Study to assess the safety and effects of cells injected intravitreal in dry macular. A quick Google search calls the trial up, along with the name of the company responsible: Bioheart Inc., otherwise known as US Stem Cell. As the ClinicalTrials.gov page indicates, the study has been withdrawn prior to enrollment. According to Goldberg and Albini, the company is no longer performing the procedure, but it is still seeing patients.

The trial itself was a joke, lacking in all the components of a properly designed test. It wasnt based on prior laboratory experiments, no control group was assigned, no data was collected, and no plans were made for follow-ups.

During the procedure, the patients had some of their fat cells (i.e. adipose tissue) removed, along with a standard blood withdrawal. The fat tissues were then processed with an enzyme to draw out stem cells. Once plasma was isolated from the blood and added to the stem cells, the mixture was injected into both eyes of each patientyes, both eyes. Again, another serious clinical no-no; normally, only one eye would be injected for an experimental procedure like this in the event that something should go wrong. The entire procedure lasted less than an hour.

A week later, all three women were blind. As noted in the NEJM report, the blindness was accompanied by detached retinas and hemorrhaging.

The patients severe visual loss after the injection was associated with ocular hypertension, hemorrhagic retinopathy, vitreous hemorrhage, combined traction and rhegmatogenous retinal detachment, and lens dislocation. After one year, the patients visual acuity ranged from 20/200 to no light perception.

Goldberg and Albini say the preparation of the stem cells was likely shoddy, and the injections may have been contaminated. Once in the eye, the stem cells could have changed into myofibroblasts, a type of cell associated with scarring.

The Florida clinic, it would appear, was appealing to the desperation of their patients, while taking advantage of a regulatory loophole. As the authors write in their report:

Adipose tissuederived stem cells have been increasingly used by stem-cell clinics because of the relative ease of obtaining and preparing these cells. Many of the clinics that provide these stem-cell therapies have done so under the auspices of patient-funded, institutional review boardapproved research, and the research is listed on ClinicalTrials.gov without an investigational new drug filing with the FDA.

At the time, the procedure was not subject to FDA approval because the cells werent transferred between patients, and because the cells were considered minimally processed. The FDA has since revised its requirements, and it now needs approval for these types of procedures. In addition to updating its regulations, the FDA is also clamping down on stem cell clinics.

Thats obviously a good thing, but its a little too late for the women involved. This incident shows what happens when regulations and oversight are weak, and how shady companies will take risks with their patients health. Certainly food for thought as Trump and his cronies start to recreate the FDA in their own image.

Update: We reached out to US Stem Cell Clinic for comment and they responded with this statement:

Founded in 1999, U.S Stem Cell, Inc. has been committed to the research and development of effective cell technologies to treat patients with a variety of diseases and injuries. Since 2001, our clinics have successfully conducted more than 7,000 stem cell procedures with less than 0.01% adverse reactions reported. We are unable to comment further on specific cases due to patient confidentiality or legal confidentiality obligations. Neither US Stem Cell nor US Stem Cell Clinic currently treats eye patients.

[New England Journal of Medicine]

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Florida Clinic Blinds Three Patients in Botched 'Clinical Trial' - Gizmodo

Bone Marrow Stem Cells Comments Off on Florida Clinic Blinds Three Patients in Botched ‘Clinical Trial’ – Gizmodo | March 16th, 2017

For Release: March 15, 2017 Contact: Grove Potter, mpotter3@buffalo.edu University at Buffalo 716-645-2130 From skin to brain: Stem cells without genetic modification

UB study yields neural crest cells from adult skin cells, and could lead to new treatments for Parkinsons and other brain illnesses

BUFFALO, N.Y. A discovery, several years in the making, by a University at Buffalo research team has proven that adult skin cells can be converted into neural crest cells (a type of stem cell) without any genetic modification, and that these stem cells can yield other cells that are present in the spinal cord and the brain.

The applications could be very significant, from studying genetic diseases in a dish to generating possible regenerative cures from the patients own cells.

Its actually quite remarkable that it happens, says Stelios T. Andreadis, PhD, professor and chair of UBs Department of Chemical and Biological Engineering, who recently published a paper on the results in the journal Stem Cells.

The identity of the cells was further confirmed by lineage tracing experiments, where the reprogrammed cells were implanted in chicken embryos and acted just as neural crest cells do.

Stem cells have been derived from adult cells before, but not without adding genes to alter the cells. The new process yields neural crest cells without addition of foreign genetic material. The reprogrammed neural crest cells can become smooth muscle cells, melanocytes, Schwann cells or neurons.

In medical applications this has tremendous potential because you can always get a skin biopsy, Andreadis says. We can grow the cells to large numbers and reprogram them, without genetic modification. So, autologous cells derived from the patient can be used to treat devastating neurogenic diseases that are currently hampered by the lack of easily accessible cell sources.

The process can also be used to model disease. Skin cells from a person with a genetic disease of the nervous system can be reprogrammed into neural crest cells. These cells will have the disease-causing mutation in their chromosomes, but the genes that cause the mutation are not expressed in the skin. The genes are likely to be expressed when cells differentiate into neural crest lineages, such as neurons or Schwann cells, thereby enabling researchers to study the disease in a dish. This is similar to induced pluripotent stem cells, but without genetic modification or reprograming to the pluripotent state.

The discovery was a gradual process, Andreadis says, as successive experiments kept leading to something new. It was one step at a time. It was a very challenging task that took almost five years and involved a wide range of expertise and collaborators to bring it to fruition, Andreadis says. Collaborators include Gabriella Popescu, PhD, professor in the Department of Biochemistry in the Jacobs School of Medicine and Biomedical Sciences at UB; Song Liu, PhD, vice chair of biostatistics and bioinformatics at Roswell Park Cancer Institute and a research associate professor in biostatistics UBs School of Public Health and Health Professions; and Marianne Bronner, PhD, professor of biology and biological engineering, California Institute of Technology.

Andreadis credits the persistence of his then-PhD student, Vivek K. Bajpai, for sticking with it.

He is an excellent and persistent student, Andreadis says. Most students would have given up. Andreadis also credits a seed grant from UBs office of the Vice President for Research and Economic Developments IMPACT program that enabled part of the work. The work recently received a $1.7 million National Institutes of Health grant to delve into the mechanisms that occur as the cells reprogram, and to employ the cells for treating the Parkinsons-like symptoms in a mouse model of hypomyelinating disease. This work has the potential to provide a novel source of abundant, easily accessible and autologous cells for treatment of devastating neurodegenerative diseases. We are excited about this discovery and its potential impact and are grateful to NIH for the opportunity to pursue it further, Andreadis said.

The research, described in the journal Stem Cells under the title Reprogramming Postnatal Human Epidermal Keratinocytes Toward Functional Neural Crest Fates, was supported by grants from the National Institutes of Health.

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From Skin to Brain: Stem Cells Without Genetic Modification

Skin Stem Cells Comments Off on From Skin to Brain: Stem Cells Without Genetic Modification | March 16th, 2017

A discovery, several years in the making, by a University at Buffalo research team has proven that adult skin cells can be converted into neural crest cells (a type of stem cell) without any genetic modification, and that these stem cells can yield other cells that are present in the spinal cord and the brain.

The practical implications could be very significant, from studying genetic diseases in a dish to generating possible regenerative cures from the patient's own cells.

"It's actually quite remarkable that it happens," said Stelios T. Andreadis, Ph.D., professor and chair of UB's Department of Chemical and Biological Engineering, who recently published a paper on the results in the journal Stem Cells.

The identity of the cells was further confirmed by lineage tracing experiments, where the reprogrammed cells were implanted in chicken embryos and acted just as neural crest cells do.

Stem cells have been derived from adult cells before, but not without adding genes to alter the cells. The new process yields neural crest cells without addition of foreign genetic material. The reprogrammed neural crest cells can become smooth muscle cells, melanocytes, Schwann cells or neurons.

"In medical applications this has tremendous potential because you can always get a skin biopsy," Andreadis said. "We can grow the cells to large numbers and reprogram them, without genetic modification. So, autologous cells derived from the patient can be used to treat devastating neurogenic diseases that are currently hampered by the lack of easily accessible cell sources."

The process can also be used to model disease. Skin cells from a person with a genetic disease of the nervous system can be reprogrammed into neural crest cells. These cells will have the disease-causing mutation in their chromosomes, but the genes that cause the mutation are not expressed in the skin. The genes are likely to be expressed when cells differentiate into neural crest lineages, such as neurons or Schwann cells, thereby enabling researchers to study the disease in a dish. This is similar to induced pluripotent stem cells, but without genetic modification or reprograming to the pluripotent state.

The discovery was a gradual process, Andreadis said, as successive experiments kept leading to something new. "It was one step at a time. It was a very challenging task that took almost five years and involved a wide range of expertise and collaborators to bring it to fruition," Andreadis said. Collaborators include Gabriella Popescu, Ph.D., professor in the Department of Biochemistry in the Jacobs School of Medicine and Biomedical Sciences at UB; Song Liu, Ph.D., vice chair of biostatistics and bioinformatics at Roswell Park Cancer Institute and a research associate professor in biostatistics UB's School of Public Health and Health Professions; and Marianne Bronner, Ph.D., professor of biology and biological engineering, California Institute of Technology.

Andreadis credits the persistence of his then-Ph.D. student, Vivek K. Bajpai, for sticking with it.

"He is an excellent and persistent student," Andreadis said. "Most students would have given up." Andreadis also credits a seed grant from UB's office of the Vice President for Research and Economic Development's IMPACT program that enabled part of the work.

The work recently received a $1.7 million National Institutes of Health grant to delve into the mechanisms that occur as the cells reprogram, and to employ the cells for treating the Parkinson's-like symptoms in a mouse model of hypomyelinating disease.

"This work has the potential to provide a novel source of abundant, easily accessible and autologous cells for treatment of devastating neurodegenerative diseases. We are excited about this discovery and its potential impact and are grateful to NIH for the opportunity to pursue it further," Andreadis said.

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From Skin to Brain: Stem Cells Without Genetic Modification - Bioscience Technology

Skin Stem Cells Comments Off on From Skin to Brain: Stem Cells Without Genetic Modification – Bioscience Technology | March 16th, 2017

Studying brain disorders is complicated for many reasons, not the least being the ethics of obtaining living neurons. To overcome that obstacle, UC San Francisco postdoc Aditi Deshpande, PhD, is starting with skin cells.

Thanks to developments in stem cell technology, new information about the human brain is now being gleaned from a simple cheek swab or skin sample. This technology is key to the kind of progress Despande and researchers like her are making. It allows them to work with cells otherwise unobtainable living brain cells that have the same genetics as the patients.

Deshpande begins with skin cells obtained from the Simons Foundation from volunteers whose DNA contains a specific deletion or duplication of one chromosome. She cultures these cells and then turns them into induced pluripotent stem cells cells that have been coaxed back to their embryonic state and are able to become any other type of cell. From there, she reprograms them to become a specific type of neuron thats involved in attention and information processing.

The deletion or duplication Deshpande is looking for stems from a 2008 finding by Lauren Weiss, PhD, an associate professor of neurology in the UCSF Department of Psychiatry and the UCSF Institute for Human Genetics.

Weiss discovered a 29-gene region of DNA on chromosome 16 that is associated with autism, seizures and other brain disorders. Normally, a person has two copies of the region one on each copy of chromosome 16. In some of Deshpandes samples, the region is deleted from one chromosome, leaving one copy. In others, the region is duplicated, resulting in three copies. Subjects with only one copy of the region were more likely to have macrocephaly an enlarged brain than a typical subject, and those with three copies were more likely to have microcephaly a smaller brain.

Whats really interesting, said Deshpande, is that although these subjects seem to have opposite features in terms of brain size, we see a related effect, based on whether they have fewer or more copies of the region.

Some known models of autism show a connection between a neurons growth or appearance and macrocephaly, she explained. We wanted to know if the same thing is happening here.

To compare the effect of the mutation, Deshpande first stains the obtained skin cells so that she can visualize the neurons under a microscope. After staining, Deshpande used cell-counting software to assess several thousands of neurons from deletion and duplication samples and measure them against normal neurons. She found that the neurons missing the DNA region exhibited some differences compared to typical neurons.

Her next step in her research is to discern which of the regions 29 genes are involved in these differences.

The work is meticulous, but Deshpande doesnt mind. I simply love looking at neurons, she said. It really makes you appreciate the complexity of the brain.

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Science in Focus: Creating Neurons from Skin Cells to Understand Autism - UCSF News Services

Skin Stem Cells Comments Off on Science in Focus: Creating Neurons from Skin Cells to Understand Autism – UCSF News Services | March 16th, 2017

NetDugout

Some genetic variations difficult to evaluate using current stem cell modeling techniques Science Daily Stem cell-based disease modeling involves taking cells from patients, such as skin cells, and introducing genes that reprogram the cells into human-induced pluripotent stem cells (hiPSCs). These "master cells" are unspecialized, meaning they can be ... Would You Slather Blood and Breast Milk on Your Face?Racked all 19 news articles »

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Some genetic variations difficult to evaluate using current stem cell modeling techniques - Science Daily

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Scientists have long hoped that stem cells might have the power to treat diseases. But it's always been clear that they could be dangerous too, especially if they're not used carefully.

Now a pair of papers published Wednesday in the New England Journal of Medicine is underscoring both the promise and the peril of using stem cells for therapy.

In one report, researchers document the cases of three elderly women who were blinded after getting stem cells derived from fat tissue at a for-profit clinic in Florida. The treatment was marketed as a treatment for macular degeneration, the most common cause of blindness among the elderly. Each woman got cells injected into both eyes.

In a second report, a patient suffering from the same condition had a halt in the inexorable loss of vision patients usually experience, which may or may not have been related to the treatment. That patient got a different kind of stem cell derived from skin cells as part of a carefully designed Japanese study.

The Japanese case marks the first time anyone has given induced pluripotent stem (iPS) cells to a patient to treat any condition.

"These two reports are about as stark a contrast as it gets," says George Q. Daley, Harvard Medical School's dean and a leading stem cell researcher. He wrote an editorial accompanying the two papers. "It's really striking."

The report about the three women in their 70s and 80s who were blinded in Florida is renewing calls for the Food and Drug Administration to crack down on the hundreds of clinics that are selling unproven stem cell treatments for a wide variety of medical conditions, including arthritis, autism and stroke.

"One of the big mysteries about this particular case and the mushrooming stem cell clinic industry more generally is why the FDA has chosen to effectively sit itself out on the sidelines even as this situation overall grows increasingly risky to patients," says Paul Knoepfler, a University of California, Davis, stem cell researcher who has studied the proliferation of stem cell clinics.

"The inaction by the FDA not only puts many patients at serious risk from unproven stem cell offerings, but also it undermines the agency's credibility," Knoepfler wrote in an email.

In response to a query from Shots, an FDA spokeswoman wrote in an email that the agency is in the process of finalizing four new guidelines aimed at clarifying how clinics could use stem cells as treatments. The agency also noted that it had previously issued a warning to patients.

In the meantime, "consumers are encouraged to contact FDA and the appropriate state authorities in their jurisdictions to report any potentially illegal or harmful activity related to stem cell based products," the FDA email says.

Other researchers say the cases should stand as a warning to patients considering unproved stem cell treatments, especially those tried outside carefully designed research studies.

"Patients have to be wary and tell the difference between the snake oil salesmen who are going to exploit them and the kind of slow, painstaking legitimate clinical trials that are also going on," Daley says.

The New England Journal of Medicine report did not name the Florida clinic, but noted that the treatment was listed on a government website that serves as a clearinghouse for research studies. The sponsor is listed as Bioheart, Inc., which is part of U.S. Stem Cell Inc. in Sunrise, Fla.

Kristen Comella, the scientific director of U.S. Stem Cell, would not discuss the cases. "There were legal cases associated with eye patients that were settled under confidentiality, so I am not permitted to speak on any details of those cases due to the confidentiality clause," Comella said by phone.

She acknowledged, however, that the clinic had been performing the stem cell procedures. They were discontinued after at least two patients suffered detached retinas, she says.

But Comella defended the use of stem cells from fat tissue to treat a wide variety of other health problems.

"We have treated more than 7,000 patients and we've have had very few adverse events reported. So the safety track record is very strong," Comella says. "We feel very confident about the procedures that we do, and we've had great success in many different indications."

According to the New England Journal of Medicine report, The Florida clinic was using adult stem cells, which circulate in various parts of the body, including in fat tissue. While those cells may someday be turn out to be useful for treating disease, none have been proven to work.

The body produces a variety of stem cells. The kind that have generated the most excitement and controversy are human embryonic stem cells, which are derived from early human embryos and can be coaxed to become any kind of cell in the body.

Scientists are also excited about iPS cells, which can be made in the laboratory by turning any cell in the body, such as skin cells, into cells that resemble embryonic stem cells.

Those are the cells that were tested by the Japanese scientists. The stem cells were converted into retinal pigment epithelium (RPE) cells, which are the cells that are destroyed by macular degeneration.

"This represents a landmark," says Daley. "It's the first time any patient has been treated with cellular derivatives of iPS cells. So it's definitely a world first."

Daley noted that the scientists only treated one of the patient's eyes in case something went wrong, to ensure remaining vision would not be threatened in the other eye.

After at least a year, no complications had occurred and the patient had not experienced any further deterioration of vision in the treated eye. While that is promising, more patients would have to be treated and followed for much longer to know whether that approach is successful, Daley says.

"Given that macular degeneration is the most frequent cause of vision loss and blindness in the elderly and our population is aging, the prevalence of macular degeneration is going up dramatically," Daley says. "So to be able to preserve or even restore sight would be a really remarkable medical advance."

Despite the potentially encouraging results with the first patient, Daley noted that the Japanese scientists decided not to treat a second patient and suspended the study. That's because they discovered worrisome genetic variations in the RPE cells they had produced for the second patient.

"They weren't certain these would cause problems for the patient, but they were restrained enough and cautious enough that they decided not to go forward," Daley says. "That's what contrasts so markedly with the approach of the second group, who treated the three patients with an unproven stem cell therapy that ended up have devastating effects on their vision."

In this case, the New England Journal of Medicine report says, patients paid $5,000 each to receive injections of solutions that supposedly contained stem cells that were obtained from fat removed from their abdomens through liposuction.

Even though the safety and effectiveness of this procedure is unknown, all three patients received injections in both eyes.

"That's what led to these horrible results," says Thomas Albini, a retina specialist at the University of Miami's Bascom Palmer Eye Institute, who helped write the report.

Before the procedure, all three women still had at least some vision. Afterwards, one woman was left completely blind while the other two were effectively blind, Albini and his colleagues reported.

The cases show that patients need to be warned that something that "sounds too good to be true may indeed be too good to be true and may even be horrible," Albini says.

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3 Women Blinded By Unproven Stem Cell Treatments - NPR

IPS Cell Therapy Comments Off on 3 Women Blinded By Unproven Stem Cell Treatments – NPR | March 16th, 2017

Monday, March 13, 2017 3 a.m. CDT

BRUSSELS (Reuters) - Belgian biotech group Tigenix said on Monday its medical trial with a novel treatment for patients at risk of heart failure after a coronary attack was successful.

The group said patients treated in its PhaseI/II trial of donor-derived expanded cardiac stem cells (AlloCSC) showed no side-effects and all of them continued to live after 30 days, six months and a year.

Tigenix added that in one subgroup of trial patients associated with a poor long-term outlook, there was a larger reduction in the size of infarction, tissue death due to inadequate blood supply.

"This is the first trial in which it has been demonstrated that allogeneic cardiac stem cells can be transplanted safely through the coronary tree," one of the doctors in the trial said.

The group said it would now analyze the data from the trial and decide on how to proceed with its research.

(Reporting by Robert-Jan Bartunek; editing by Philip Blenkinsop)

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Belgium's Tigenix says heart attack stem cell trial successful - KFGO

Cardiac Stem Cells Comments Off on Belgium’s Tigenix says heart attack stem cell trial successful – KFGO | March 15th, 2017

Runner's World

Stem Cell Therapy Runner's World This is why researchers and physicians think this therapy may help joint injuries caused by worn-out cartilage; in cell cultures, stem cells can grow new cartilage, and if this can happen in a joint, it may prevent the need for a joint replacement ... Nutrients Boost Stem Cell FunctionProHealth all 19 news articles »

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Stem Cell Therapy - Runner's World

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"The impact of Alzheimer's disease is vast, far exceeding the medical community's current ability to treat it," said Joshua M. Hare, M.D., Longeveron's Co-Founder and Chief Science Officer. "Regenerative medicine and cell-based therapies offer a promising new approach to close this gap and address the urgent need for effective therapies to combat the condition."

An important component in the progression of Alzheimer's disease is neuroinflammation. Longeveron was recently awarded a $1 million Part the Cloud Challenge on Neuroinflammation grant from the Alzheimer's Association to help support this research.

"Adult stem cells are very potent anti-inflammatories. The characteristic amyloid plaques found in the brains of Alzheimer's disease patients produce inflammation, and stem cells can reduce inflammation," explained Bernard S. Baumel, M.D., Principal Investigator for the trial. "Alzheimer's also impairs the brain's ability to adequately produce new brain cells in the memory area known as the hippocampus. Stem cells can stimulate the brain to produce these new cells needed to form memory. We believe that an infusion of LMSCs may improve the condition or at least halt the progression of the disease."

Prior research shows that adult MSCs target and reduce inflammation, promote tissue repair and improve brain function in mouse models of Alzheimer's disease. Longeveron's trial is the first U.S. clinical study of exogenously administered mesenchymal stem cells derived from the bone marrow of healthy adult donors for treating Alzheimer's disease.

To learn about participating in the clinical trial, visit: https://clinicaltrials.gov/ct2/show/NCT02600130

About Longeveron

Longeveron is a regenerative medicine therapy company founded in 2014. Longeveron's goal is to provide the first of its kind biological solution for aging-related diseases, and is dedicated to developing safe cell-based therapeutics to revolutionize the aging process and improve quality of life. The company's research focus areas include Alzheimer's disease, Aging Frailty and the Metabolic Syndrome. Longeveron produces LMSCs in its own state-of-the-art cGMP cell processing facility. http://www.longeveron.com

Contact: Suzanne Liv Page spage@longeveron.com 305.342.9590

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/longeveron-achieves-milestone-in-groundbreaking-stem-cell-trial-for-alzheimers-disease-300424206.html

SOURCE Longeveron

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Longeveron Achieves Milestone in Groundbreaking Stem Cell Trial for Alzheimer's Disease - PR Newswire (press release)

Bone Marrow Stem Cells Comments Off on Longeveron Achieves Milestone in Groundbreaking Stem Cell Trial for Alzheimer’s Disease – PR Newswire (press release) | March 15th, 2017

Adam Krief, with his wife, Lia, had a rare form of blood cancer that proved to be fatal. (Facebook)

(JTA) Adam Krief, a Jewish cancer patient whose search for a bone marrow donor captured the attention of social media and celebrities including Kim Kardashian, Mayim Bialik and Jason Biggs, has died.

Krief, a father of three from Los Angeles, died Tuesday, a family friend confirmed to JTA. He was 32.

Krief was diagnosed with primary myelofibrosis, a rare form of blood cancer that is likely fatal if a stem celltransplant matchis notfound.To find anHLA, or gene complex matchfor Krief something more difficultto track downthan a blood type match drives were held around the world, including in North America,Israel, France and Mexico.

Kardashian posted about Krief on Facebook in September, saying he was a friend of a friend.

A bone-marrow donor was found last December seven matches were found, in fact, through the donor drives organized for him.

This is what cloud 9 looks like Im so grateful to let you all know that a donorhas been found, Krief wrote at the time, sharing a video with two of his children.

The Hope 4 Adam Facebook page on March 8 called for a Worldwide Unity Shabbat for March 11 and March 18 for the recovery of Krief, asking followers to Help us bring about a miracle.

On Monday, the Eretz Kabbalah Facebook page of the Los Angeles-based Eretz Cultural Center posted a call for followers to recite Tehillim, or psalms, on behalf of Krief.

After a long search for a bone-marrow match to save his life, he finally received one. However, after some complications, he is said to only have a few hours to live, the post said.

Krief is survived by his wife, Lia, and his young children.

RELATED:

Jewish cancer patient finds bone marrow transplant following worldwide search, Kim Kardashians pitch

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Adam Krief, Jewish father of 3 whose bone marrow search inspired celebrities, dies - Jewish Telegraphic Agency

Bone Marrow Stem Cells Comments Off on Adam Krief, Jewish father of 3 whose bone marrow search inspired celebrities, dies – Jewish Telegraphic Agency | March 15th, 2017

A longtime product developer is bringing a peptide ingredient to the US market that has been researched for a unique property promoting the growth of bone marrow stem cells.

Called DH Stemogen, the product is the brainchild of Dr Marvin Heuer MD who has a history of product development with sports nutrition company MuscleTech. Dr. Heuer has a background in clinical research, having spent many years in drug development at Glaxo Smith Kline. He also runs a contract research firm, Heuer M.D. Research Inc. and is the CEO of omega-3 supplement manufacturer Blue Ocean Nutrascience.

The new product, called DH Stemogen is based on a Cyclo-{L-ALA-L-GLU(TRP-OH) peptide that was developed by a Russian biochemist.

Its a peptide that is a mimic of a naturally occurring thymic peptide,Dr. Heuer told NutraIngredients-USA. Heuer was promoting the launch of the product at the recent Expo West trade show in Anaheim, CA. At Heuer M.D. Research, as a company we are out looking for novel ingredientsto bring out, hopefully in the nutraceutical area.

We got interested in Prof. Vlad Deigins peptide research, Dr. Heuer said (Deigin is associated with the Institute of Bioorganic Chemistry at the Russian Academy of Sciences in Moscow.)We looked at this particular compound that he was launching as an ingredient in Russia about a year ago.

The peptide in DH Stemogen targets a particular type of stem cell hematopoietic cells (HSC). Stem cells in general are the building blocks of our bodies. These cells are able to transform themselves into almost any type of cell. There are various sources of stem cells in an adult body. One of the most important of them comprises the bone marrow, where the HSCs are produced. HSCs transform into all the main cell types in our blood, including red blood cells and white blood cells. Dr. Heuer said there is some evidence that those cells are able to reconstruct other body tissues by transforming into the specific tissue type cell such as liver, nervous tissue, kidney and skin.

These properties would seem to make Stemogen a natural for a healthy aging product positioning, Dr. Heuer said. But Deigins research, trending as it does over into disease endpoints, is a little problematical when it comes to supporting US-style structure function claims, he admitted. Other countries dont make the same hard and fast distinctions between dietary ingredients meant for supplement applications and active pharmaceutical agents meant for drugs, he said.

We are going to be very cautious about making structure/function claims,Dr. Heuer said. The product at the moment saysSupport your immune system and Support healthy levels of stem cells in your blood.

We are about to begin a whole profile of research in the U.S. and Canada, he added.

Dr. Heuer said one thing thats unique about the ingredient (and something that he says Deigin has patented) is a structural twist that improves the peptides stability. The criticism of some other novel peptides has been that interesting as their properties might be, once they hit the stomachs gastric fluid they blow apart into their constituent amino groups and all those novel properties are lost.

He has a patent on the way he makes this with a hex ring on the end that protects it in the GI tract and allows it to be absorbed,he said.

Bringing a synthetic analogue of a naturally occurring peptide to market as a dietary ingredient would seem to pose significant regulatory challenges. Dr. Heuer said hes confident there is a way through that thicket. The plan is to start first with a GRAS filing, and Dr. Heuer said he believes that the peptide would fall under the amino acid category in the DHSEA definitions of what constitutes a dietary ingredient.

Certainly there is a precedent of complex peptides being sold on the market, he said.

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Peptide aimed at stem cell genesis debuts on supplement market - NutraIngredients-usa.com

Bone Marrow Stem Cells Comments Off on Peptide aimed at stem cell genesis debuts on supplement market – NutraIngredients-usa.com | March 15th, 2017

Adam Krief, a Jewish cancer patient whose search for a bone marrow donor captured the attention of social media and celebrities including Kim Kardashian, Mayim Bialik and Jason Biggs, has died.

Krief, a father of three from Los Angeles, died Tuesday, a family friend confirmed to JTA. He was 31.

Krief was diagnosed with primary myelofibrosis, a rare form of blood cancer that is likely fatal if a stem cell transplant match is not found. To find an HLA, or gene complex match for Krief something more difficult to track down than a blood type match drives were held around the world, including in North America, Israel, France and Mexico.

Kardashian posted about Krief on Facebook in September, saying he was a friend of a friend.

A bone-marrow donor was found last December seven matches were found, in fact, through the donor drives organized for him.

This is what cloud 9 looks like Im so grateful to let you all know that a donor has been found, Krief wrote at the time, sharing a video with two of his children.

The Hope 4 Adam Facebook page on March 8 called for a Worldwide Unity Shabbat for March 11 and March 18 for the recovery of Krief, asking followers to Help us bring about a miracle.

On Monday, the Eretz Kabbalah Facebook page of the Los Angeles-based Eretz Cultural Center posted a call for followers to recite Tehillim, or psalms, on behalf of Krief.

After a long search for a bone-marrow match to save his life, he finally received one. However, after some complications, he is said to only have a few hours to live, the post said.

Krief is survived by his wife, Lia, and his young children.

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American Jewish father of 3 whose bone marrow search inspired celebrities dies - Jerusalem Post Israel News

Bone Marrow Stem Cells Comments Off on American Jewish father of 3 whose bone marrow search inspired celebrities dies – Jerusalem Post Israel News | March 15th, 2017

The first new finding is an obvious onethe mouse experiments worked in human cells. Just because something worked in mice doesn't necessarily mean it will work in people too. So this is a really important finding.

The second important finding has to do with the specific genes each group used. Both groups added four genes to turn a stem cell into an ES cell. But they used a slightly different set of genes.

The Japanese group added OCT3/4, SOX2, KLF4, and c-MYC. The Wisconsin group added OCT4, SOX2, NANOG, and LIN28. This matters because of a side effect seen in the previous mouse study.

The mouse study went farther than the human study in that the researchers added these new ES cells to a mouse embryo. The results were disconcerting. Around 20% of the mice developed cancer from the cells. The researchers hypothesized that the cause was one or more of the genes that were used to create the ES cell.

By using different sets of genes in the human cell study, the researchers showed you don't need the same four genes to create an ES cell. The hope is that the researchers will find a combination of genes that do not cause cancer.

Once the scientists find a set of genes that don't cause cancer, this research should blow the stem cell field wide open. We still don't know if ES cells will work to actually cure disease. But ethical ES cells should open the spigot of federal funds so American scientists can finally research this subject to its full extent. Then we'll see if ES cells can really live up to their hype. Or if we need to pursue other ways to cure these illnesses.

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Human Embryonic Stem (ES) Cells from Skin Cells ...

Skin Stem Cells Comments Off on Human Embryonic Stem (ES) Cells from Skin Cells … | March 15th, 2017

March 15, 2017 by Grove Potter The four images, from left to right, show Keratinocyte-derive neural crest stem cells turning into neurons as shown by typical neuronal morphology. Credit: University at Buffalo.

A discovery, several years in the making, by a University at Buffalo research team has proven that adult skin cells can be converted into neural crest cells (a type of stem cell) without any genetic modification, and that these stem cells can yield other cells that are present in the spinal cord and the brain.

The practical implications could be very significant, from studying genetic diseases in a dish to generating possible regenerative cures from the patient's own cells.

"It's actually quite remarkable that it happens," says Stelios T. Andreadis, PhD, professor and chair of UB's Department of Chemical and Biological Engineering, who recently published a paper on the results in the journal Stem Cells.

The identity of the cells was further confirmed by lineage tracing experiments, where the reprogrammed cells were implanted in chicken embryos and acted just as neural crest cells do.

Stem cells have been derived from adult cells before, but not without adding genes to alter the cells. The new process yields neural crest cells without addition of foreign genetic material. The reprogrammed neural crest cells can become smooth muscle cells, melanocytes, Schwann cells or neurons.

"In medical applications this has tremendous potential because you can always get a skin biopsy," Andreadis says. "We can grow the cells to large numbers and reprogram them, without genetic modification. So, autologous cells derived from the patient can be used to treat devastating neurogenic diseases that are currently hampered by the lack of easily accessible cell sources."

The process can also be used to model disease. Skin cells from a person with a genetic disease of the nervous system can be reprogrammed into neural crest cells. These cells will have the disease-causing mutation in their chromosomes, but the genes that cause the mutation are not expressed in the skin. The genes are likely to be expressed when cells differentiate into neural crest lineages, such as neurons or Schwann cells, thereby enabling researchers to study the disease in a dish. This is similar to induced pluripotent stem cells, but without genetic modification or reprograming to the pluripotent state.

The discovery was a gradual process, Andreadis says, as successive experiments kept leading to something new. "It was one step at a time. It was a very challenging task that took almost five years and involved a wide range of expertise and collaborators to bring it to fruition," Andreadis says. Collaborators include Gabriella Popescu, PhD, professor in the Department of Biochemistry in the Jacobs School of Medicine and Biomedical Sciences at UB; Song Liu, PhD, vice chair of biostatistics and bioinformatics at Roswell Park Cancer Institute and a research associate professor in biostatistics UB's School of Public Health and Health Professions; and Marianne Bronner, PhD, professor of biology and biological engineering, California Institute of Technology.

Andreadis credits the persistence of his then-PhD student, Vivek K. Bajpai, for sticking with it.

"He is an excellent and persistent student," Andreadis says. "Most students would have given up." Andreadis also credits a seed grant from UB's office of the Vice President for Research and Economic Development's IMPACT program that enabled part of the work.

The work recently received a $1.7 million National Institutes of Health grant to delve into the mechanisms that occur as the cells reprogram, and to employ the cells for treating the Parkinson's-like symptoms in a mouse model of hypomyelinating disease.

"This work has the potential to provide a novel source of abundant, easily accessible and autologous cells for treatment of devastating neurodegenerative diseases. We are excited about this discovery and its potential impact and are grateful to NIH for the opportunity to pursue it further," Andreadis said.

The research is described in the journal Stem Cells under the title "Reprogramming Postnatal Human Epidermal Keratinocytes Toward Functional Neural Crest Fates."

Explore further: Embryonic gene Nanog reverses aging in adult stem cells

More information: Vivek K. Bajpai et al, Reprogramming Postnatal Human Epidermal Keratinocytes Toward Functional Neural Crest Fates, STEM CELLS (2017). DOI: 10.1002/stem.2583

Journal reference: Stem Cells

Provided by: University at Buffalo

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Caltech scientists have converted cells of the lower-body region into facial tissue that makes cartilage, in new experiments using bird embryos. The researchers discovered a "gene circuit," composed of just three genes, that ...

Scientists at the University of Newcastle, UK, have used a combination of small molecules to turn cells isolated from human skin into Schwann cells - the specialised cells that support nerves and play a role in nerve repair. ...

Johns Hopkins stem cell biologists have found a way to reprogram a patient's skin cells into cells that mimic and display many biological features of a rare genetic disorder called familial dysautonomia. The process requires ...

(Phys.org)A team of researchers affiliated with New York and Dalhousie Universities, in the U.S. and Canada respectively, has found a possible intermediate cell type that might help understand the evolutionary process ...

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New research led by the UK's Centre for Ecology & Hydrology has revealed for the first time that flower-rich habitats are key to enhancing the survival of bumblebee families between years.

A discovery, several years in the making, by a University at Buffalo research team has proven that adult skin cells can be converted into neural crest cells (a type of stem cell) without any genetic modification, and that ...

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From skin to brain: Stem cells without genetic modification - Phys.Org

Skin Stem Cells Comments Off on From skin to brain: Stem cells without genetic modification – Phys.Org | March 15th, 2017

RenovaCare Inc. (OTCQB:RCAR) is a New York City-based biotechnology company developing its patented CellMist and SkinGun stem cell technologies for treating burns in weeks or less as well as treating chronic and acute wounds, acne scarring, and skin defects and diseases. In December, it received a U.S. patent for its SkinGun device.

Before joining RenovaCare, CEO Thomas Bold was CEO of StemCell Systems. He has more than 15 years of experience in medical biotechnology device manufacturing and stem cell platform development.

Harlan Levy: How does your CellMist technology specifically work?

Thomas Bold: Doctors isolate a high concentration of the most desirable stem cell population from a very small donor sample of the patient's own skin and suspended in the liquid CellMist Solution. It's then gently sprayed onto wound sites using our SkinGun, which looks like Captain Kirk's particle-beam gun, the "Phaser" in the Star Trek TV series.

The isolated cells include cells that proliferate rapidly in order to achieve quick re-epithelialization. This is the stage at which a burn is technically considered "healed" and patients are often discharged. The average person would recognize this healing phase as the point at which the wound develops a thin, shiny, pink-colored protective layer.

H.L.: What are existing burn treatments, and how do they compare with the SkinGun treatment?

T.B.: Traditional skin grafting has been the treatment for burns and wounds for centuries. More recently, mesh grafting has become the latest standard of care. This process surgically removes large sheets of healthy skin from the patient. Following this painful donor procedure, the sheet is punctured in a grid-like pattern to form an expandable mesh. Surgeons pull this mesh as wide as feasible and surgically stitch this skin to the patient's wound. The procedure is extremely painful, creates an additional wound at each donor site and results in poor cosmetic outcomes, often with scarred and deformed skin.

This transplanted skin can result in restricted joint movement and is unable to grow with the patient. Consequently, mesh graft patients require months and sometimes up to a year of physical therapy and can face psychological problems from the permanent disfigurement of scarring. In addition, long-term pain management with painkillers is very often necessary.

With the RenovaCare treatment technology, by spraying the patient's stem cells, the SkinGun overcomes the need for removing large sheets of donor skin, and the resultant healing does not require prolonged physical therapy. The spray procedure is gentle, and the skin that regrows looks, feels, and functions as the original skin that it replaces. Most often the healing process takes only a week.

It's very important to note here that a sheet of meshed skin covers only up to six times its original donor area. The RenovaCare system covers up to 100 times its donor skin sample. This is why the donor skin sample can be so small compared to the injured treatment area.

H.L.: What about scars and infection potential compared with conventional treatments?

T.B.: A wound heals from the edges towards the middle. The bigger the wound, the longer this process takes. And the longer this process takes, the higher the risk of infection and scarring.

Imagine a large burn of 20, 30, 40 percent of your total body surface. With our CellMist System, the doctor sprays the patient's own stem cells with a highly regenerative capacity onto the wound and, by doing so, creates tens of thousands of little regenerative islands across the wound. These islands grow outwards, ultimately connecting to each other to create a protective epithelial skin layer that covers the wound.

Experts believe the formation of this pink-colored layer marks the moment of re-epithelization where the risk of infection is reduced and the patient's wound is effectively healed. Beyond this stage, the cosmetic healing process also happens entirely natural to produce a scar-free result where, finally, skin color, tone and pigmentation are restored.

Since the RenovaCare spray procedure uses the patient's own stem cells, there isn't the risk of tissue rejection, infection, or ongoing immuno suppression therapy.

H.L.: What results have you found for patients using the SkinGun?

T.B.: We have many examples of patients recovering from severe burns within a week or two, scar-free, and walking away with unlimited joint restrictions.

In the case of one patient with severe electrical burns to over a third of his body, we were able to spray his wounds with 23 million stem cells isolated from a tiny two-inch-by two-inch sample of his own skin. Within five days of treatment, his chest and arms were already healed. Four days later, the patient was discharged from the hospital.

It's also important to note that reconstructive surgery for burn patients is especially challenging when tackling joints in the body. To this end, the authors of a case study in the reputable journal "Burns," said, "Cell-spray grafting is also especially suitable for hands and joint areas, where prolonged times to re-epithelization may significantly impact functionality and esthetic outcome."

H.L.: What different uses does the SkinGun have beside burns?

T.B.: Currently, we are focusing on severe second-degree burns, but we see the RenovaCare technology also applicable for other indications such as cosmetic procedures targeting skin pigmentation disorders, scar treatment, and other related conditions.

Our goal is to bring to market the world's most advanced technology for skin repair using a patient's own stem cells.

H.L.: Is there a record of the SkinGun use in the States and abroad?

T.B.: Having treated 72 burn patients to date, the company's early clinical target is burns with follow-on indications, including chronic wounds and cosmetic procedures.

H.L.: How much research went into creating the SkinGun and over what time period?

T.B.: The birth of RenovaCare technology goes back to the early 2000s in Berlin, Germany. Researchers, at that time, were trying to "grow" skin by seeding stem cells inside multi-dimensional bioreactors. They soon discovered that these artificial chambers were no match for the growth of the same cells when transplanted inside a human body; thus, the birth of a concept to use a patient's own wound as a natural bioreactor.

A study published in "Advances in Plastic Surgery" highlights 19 early patients with deep dermal wound burns to the face and neck, complex three-dimensional surfaces. Researchers achieved such outstanding results using our cell spray that they refused to perform further skin grafting. Instead, surgeons adopted our founding technology as their standard of care.

Let me quote from the surgeons' study, which states

"We refuse to perform a prospective randomized study with groups in which traditional skin grafting and/or wound healing are still applied for the therapy for deep dermal burns due to the excellent results in our study. The method of CEA spray application has become our standard of care for these indications. The faster wound closure, the promotion of spontaneous wound healing by keratinocyte application, as well as the preservation of donor sites are further advantages of the method."

The same paper concluded that "using a spray technique results in excellent cosmetic outcomes compared with any other method."

H.L.: How has the technology changed since then?

T.B.: Since the time of this early approach, our technology has evolved and matured significantly. Our cell isolation no longer requires complex procedures, culturing, expansion, and processing time, and our stem cell spray device no longer requires multiple hand-assembled parts. Its independent power and flow-control unit has been condensed in size from a 2-foot cube down to a 9-volt battery placed inside the handle of a single handheld spray gun.

H.L.: What is the potential market for the technology in dollars and number of patients?

T.B.: Conservatively speaking, the market for our technology exceeds $50 billion. There are nearly a million people who suffer from burns each year in the U.S. alone. According to the American Burn Association, burn injuries continue to be one of the leading causes of accidental death and injury in the U.S, and one civilian fire death occurs every two hours and forty minutes.

H.L.: How much would you estimate the treatment cost may be for each different use?

T.B.: The SkinGun technology is currently under development and not approved for clinical use in the U.S., so it's too early to talk about what the treatment will cost. We have always been mindful of reimbursement, and nearly two years ago, we commissioned an investigation into the reimbursement pathway for our CellMist System. We know that reimbursement opportunities are available by way of current coding and practices.

We have further investigated and evaluated the "bundling" approach currently advocated for by insurers and are confident that that our technology is well placed to take advantages of any shift towards such a model.

H.L: What is the schedule to get Federal Drug Administration clearance?

T.B.: In order to achieve FDA clearance for the CellMist System and the SkinGun, we will be working to show our technology is safe and prove its efficacy within applicable clinical trial formats and according to the relevant regulatory requirements. I can't speculate as to how long the FDA clearance process will take, and, therefore, it's hard to speculate when our product will be commercialized.

H.L.: What other products are you investigating and how may they work?

T.B.: We are focusing on bringing the SkinGun and our stem cell spray technology to market at this time.

H.L.: What is your background, including age, education, prior employment?

T.B.: Before joining RenovaCare I worked as the CEO of StemCell Systems GmbH, a Berlin-based biomedical company engaged in the development and commercialization of advanced cell culture bioreactors. I have more than 15 years of professional business experience in the field of medical biotechnology device manufacturing, stem cell culture technology platform development and regenerative medicine research project management and product development. I also co-founded several start-up companies in Germany.

Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.

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.

Editor's Note: This article discusses one or more securities that do not trade on a major U.S. exchange. Please be aware of the risks associated with these stocks.

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RenovaCare: Stem Cell Treatment Heals Burns In Weeks Not Months - Seeking Alpha

Skin Stem Cells Comments Off on RenovaCare: Stem Cell Treatment Heals Burns In Weeks Not Months – Seeking Alpha | March 15th, 2017

ScienceBlog.com (blog)

Science in Focus: Creating Neurons from Skin Cells to Understand Autism ScienceBlog.com (blog) Studying brain disorders is complicated for many reasons, not the least being the ethics of obtaining living neurons. To overcome that obstacle, UC San Francisco postdoc Aditi Deshpande, PhD, is starting with skin cells. Thanks to developments in stem ... and more »

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Science in Focus: Creating Neurons from Skin Cells to Understand Autism - ScienceBlog.com (blog)

Skin Stem Cells Comments Off on Science in Focus: Creating Neurons from Skin Cells to Understand Autism – ScienceBlog.com (blog) | March 15th, 2017

March 15, 2017 Credit: Universit du Luxembourg

Stem cells are unspecialised cells that can develop into any type of cell in the human body. So far, however, scientists only partially understand how the body controls the fate of these all-rounders, and what factors decide whether a stem cell will differentiate, for example, into a blood, liver or nerve cell. Researchers from the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg and an international team have now identified an ingenious mechanism by which the body orchestrates the regeneration of red and white blood cells from progenitor cells. "This finding can help us to improve stem cell therapy in future," says Dr. Alexander Skupin, head of the "Integrative Cell Signalling" group of LCSB.

Although all cells in an organism carry the same genetic blueprints the same DNA some of them act as blood or bone cells, for example, while others function as nerve or skin cells. Researchers already understand quite well how individual cells work. But how an organism is able to create such a diversity of cells from the same genetic template and how it manages to relocate them to wherever they are needed in the body is still largely unknown. In order to learn more about this process, Alexander Skupin and his team treated blood stem cells from mice with growth hormones and then watched closely how these progenitor cells behaved during their differentiation into white or red blood cells. The researchers observed that the cells' transformation does not occur in linear, targeted fashion, but rather more opportunistically. Each progenitor cell adapts to the needs of its environment and integrates itself into the body where new cells are needed. "So, it is not as though the cell takes a ticket at the beginning of its differentiation and then travels straight to its destination. Rather, it gets off frequently to look around and see which line is best to take," Alexander Skupin explains.

By this clever mechanism, a multicellular organism can adapt the regrowth of new cells to its current needs. "Before progenitor cells differentiate once and for all, they first lose their stem cell character and then check, as it were, which cell line is currently in demand. Only then do they develop into the cell type that best suits their characteristics and which prevails in their environment," Alexander Skupin says. The researcher likens this step to a game of roulette, where the different types of cells can be thought of as the differently numbered slots in the roulette wheel that catch the ball. "When the cells lose their stem cell character, they are quasi thrown into the roulette wheel, where they first bounce around aimlessly. Only when they have found the right environment do the cells then drop into that niche like the roulette ball falling into a numbered slot and differentiate definitively." This way, the body can orchestrate its cell regeneration and at the same time prevent stem cells from being misdirected too early. "Even if a cell takes a wrong turn, it is ultimately sorted out again if its characteristics are unsuitable for the niche, or slot, it has landed in," says Skupin.

With their study, Alexander Skupin and his team have shown for the first time that a progenitor cell's fate is not clearly predetermined and does not follow a straight line. "This observation contradicts the current doctrine that stem cells are programmed to follow a certain lineage from the beginning," Alexander Skupin says. The researcher is furthermore convinced that the processes are similar for other progenitor cells. "In the lab, we have observed the same differentiation pattern in so-called iPS cells, or induced pluripotent stem cells, which can transform into many different types of cells."

This knowledge can help the researchers to improve the effectiveness of therapies in future. Stem cell therapy involves administering a patient his or her own body's stem cells in order to replace other cells that have died as a result of an affliction such as Parkinson's disease. While this promising treatment method has been intensively researched over many years, there has so far been only limited practical success in endogenous stem cell therapy. It is also highly controversial, since it is frequently accompanied by severe side effects and it cannot be ruled out that some cells might degenerate and lead to cancer. "Because we now have a better understanding of how the body influences the direction in which stem cells differentiate, we can hopefully control this process better in future," Alexander Skupin concludes.

Explore further: Genetic factors control regenerative properties of blood-forming stem cells

More information: Mitra Mojtahedi et al. Cell Fate Decision as High-Dimensional Critical State Transition, PLOS Biology (2016). DOI: 10.1371/journal.pbio.2000640

Researchers from the UCLA Department of Medicine, Division of Hematology Oncology and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA have published two studies that define how key ...

To date, it has been assumed that the differentiation of stem cells depends on the environment they are embedded in. A research group at the University of Basel now describes for the first time a mechanism by which hippocampal ...

New University of Otago research is providing fresh insights into how a patient's adult stem cells could best be used to regenerate their diseased hearts.

Though immune therapy and regenerative medicine are promising areas of research for future medical therapies, they are limited today by the difficulty of creating stem cells, and scientists around the world are searching ...

Hematopoietic stem cells (HSCs) can differentiate into all of the different types of cells that comprise the blood and immune cell lineages. HSC transplantation is the only effective treatment for certain blood disorders; ...

A*STAR researchers and colleagues have developed a method to isolate and expand human heart stem cells, also known as cardiac progenitor cells, which could have great potential for repairing injured heart tissue.

So they can't use smartphones or WiFi, but bacteria have evolved some seriously complex strategies to communicate with one another. And the resulting interactions are a delicate balance of cooperation and, in some cases, ...

New research led by the UK's Centre for Ecology & Hydrology has revealed for the first time that flower-rich habitats are key to enhancing the survival of bumblebee families between years.

A discovery, several years in the making, by a University at Buffalo research team has proven that adult skin cells can be converted into neural crest cells (a type of stem cell) without any genetic modification, and that ...

The evolution of land animals has been shaped by barriers such as oceans and mountains which have divided them and sent them down different genetic paths.

(Phys.org)A trio of researchers with Anglia Ruskin University in the U.K. and the Australian National University has found that the male fiddler crab uses its oversized claw to get the attention of a prospective mate and ...

A 60-year-old mystery has been solved by biochemists at The University of Western Australia investigating the origin of a type of digestion-inhibiting proteins thought only to exist in two plant families that contain the ...

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Researchers decipher how the body controls stem cells - Phys.Org

Skin Stem Cells Comments Off on Researchers decipher how the body controls stem cells – Phys.Org | March 15th, 2017

The Scientist

Antibody Therapy Targets Cancer Stem Cells: Study The Scientist Illustration of a cancer stem cellVIMEO, LEE HEALTHCancer stem cells (CSCs) are thought to enable tumor evolutionthey're genomically unstable, primed for metastasis, and difficult to destroy. The stem cell theory of cancer suggests that conventional ... and more »

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Antibody Therapy Targets Cancer Stem Cells: Study - The Scientist

Skin Stem Cells Comments Off on Antibody Therapy Targets Cancer Stem Cells: Study – The Scientist | March 15th, 2017

Guiding a recent tour of a Kyoto University lab, a staff member holds up a transparent container. Inside are tiny pale spheres, no bigger than peas, floating in a clear liquid. This is cartilage, explains the guide, Hiroyuki Wadahama. It was made here from human iPS cells.

A monitor attached to a nearby microscope shows a mass of pink and purple dots. This is the stuff from which the cartilage was grown: induced pluripotent stem cells, often called iPS cells. Scientists can create these seemingly magical cells from any cell in the body by introducing four genes, in essence turning back the cellular clock to an immature, nonspecialized state. The term pluripotent refers to the fact iPS cells can be reprogrammed to become any type of cell, from skin to liver to nerve cells. In this way they act like embryonic stem cells and share their revolutionary therapeutic potentialand as such, they could eliminate the need for using and then destroying human embryos. Also, iPS cells can proliferate infinitely.

They can also give rise, however, to potentially dangerous mutations, possibly including ones that lead to cancerous tumors. Thus, iPS cells are a double-edged swordtheir great promise is tempered by risk. Another problem is the high cost of treating a patient with his or her own newly reprogrammed cells. But now Japanese researchers are trying a different approach.

When Kyoto University researcher Shinya Yamanaka announced in 2006 that his lab had created iPS cells from mouse skin cells for the first time, biologists were stunned. In 2007, along with James Thomson of the University of WisconsinMadison, Yamanaka repeated the feat with human skin cells. Many hailed the opening of an entirely new field of personalized regenerative medicine. Need new liver cells? No problem. Patients could benefit from having their own cells reprogrammed into ones that could help treat disease, potentially eliminating the prospect of immune rejection. In 2012 Yamanaka shared the Nobel Prize in Physiology or Medicine with John Gurdon for discovering that mature cells can be converted to stem cells. By reprogramming human cells, scientists have created new opportunities to study diseases and develop methods for diagnosis and therapy, the Nobel judges wrote. To capitalize on the discovery, Kyoto University set up the $40-million Center for iPS Cell Research and Application (CiRA), which Yamanaka directs.

A decade after the Yamanaka teams groundbreaking discoveries, however, iPS cells have retreated from the headlines; to the layperson, progress seems scant. There has only been one clinical trial involving iPS cells, and it was halted after a transplant operation on just one patienta Japanese woman in her 70s with macular degeneration, a condition that can lead to blurry vision or partial blindness. Doctors at Kobe City Medical Center General Hospital used her skin cells to grow iPS cells, which were reprogrammed into retinal cells and implanted in her eye. The treatment stopped the degeneration but the trial was halted in 2015 because genetic mutations were detected in another batch of iPS cells intended for another patient. Regulatory changes, under which the Japanese government allowed the distribution of iPS cells for clinical use, also prompted researchers to switch the study to a more efficient process of using cells from third-party donors instead of using a patients own cells. The Japanese government has a lot of incentives to considerwere developing a new science, a new technology and also a new economic market, says CiRA spokesperson Peter Karagiannis. So theres the ethical issues, but theres also money to be made. How do we balance the two?

The Kobe clinical trial had a lot riding on it. And the setback followed a major stem cell scandal in which biologist Haruko Obokata of the Riken Center for Developmental Biology was found to have falsified data in studies, published in 2014, that claimed a new method of achieving pluripotency. Then, earlier this year, Yamanaka had to apologize at a news conference after it was discovered that a reagent used to create iPS cells at CiRA was mislabeled, which could mean the wrong reagent was used. Although the mix-up is being examined, the center has halted supplies of some of its iPS cells to researchers across Japan; the error also set back by a few years a CiRA project to produce clinical-grade platelets from iPS cells.

But Yamanaka says he remains focused on the bigger picture of iPS cells and is still optimistic they can not only help researchers but may be key to transformative clinical therapies. CiRA still has a bank of tens of millions of iPS cells that have already been reset and checked for safety, so they can be used in patient applications. In terms of regenerative medicine, things have gone quicker than I expected, Yamanaka says, adding, iPS cells have exceeded expectations because of their potential for disease modeling, which allows us to elucidate unknown disease mechanisms, and drug discovery.

Those hoping for quick clinical success should remember it takes time for revolutionary treatments to go from lab bench to bedside, says Andras Nagy, a stem cell researcher at Mount Sinai Hospitals LunenfeldTanenbaum Research Institute in Toronto, who has not been directly involved in Yamanakas work. If you fully appreciate the paradigm-shifting nature of iPS cells, tremendous progress has in fact been made over the past 10 years, says Nagy, who in 2009 established a method of creating stem cells without using viruses (which had initially been used to deliver reprogramming genes into targeted cells). By comparison, penicillin was discovered as an antibiotic in 1928, but it was not available in the clinic until the early 1940s.

Researchers in Japan are meanwhile using iPS cell technology to pave the way to better drugs. For instance, CiRAs Kohei Yamamizu recently reported developing a cellular model of the bloodbrain barrier made entirely from human iPS cells. It could become a useful tool for testing drugs for brain diseases.

All eyes, however, are back on Kobe City Medical Center General Hospital, which is resuming its retina trialthis time with iPS cells from donors instead of cells from patients themselves. Using CiRAs bank of iPS cells, there are significant time and cost savingsit could be one fifth the cost of cell preparation and patient transplant or less. The initial study, with its personalized approach, reportedly cost about $875,000 for just one patient. We plan to evaluate the efficacy of transplanting the [donor] cells and consider the feasibility of using this method as a routine treatment in the future, accessible to the wider society, study co-leader Masayo Takahashi of the RIKEN Center for Developmental Biology said at a February press conference in Kobe. Her husband Jun Takahashi, a researcher at CiRA, is also planning to use donor-derived iPS cells for a clinical applicationto help treat patients with Parkinsons disease.

Nagy admits the promise of personalized cell regeneration is probably too costly for mainstream use, and he believes genomic editingin which DNA is inserted or deletedis key to safe iPS cell implants. For his part, Yamanaka is cautiously optimistic about iPS cells as a therapeutic tool.

Regenerative medicine and drug discovery are the two key applications for iPS cells, Yamanaka says. With the use of iPS cell stock, we are now able to work quicker and cheaper, so thats the challenge going forward.

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Waiting to Reprogram Your Cells? Don't Hold Your Breath - Scientific American

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