Abnormal development of the brain in an intractable disease, thanatophoric dysplasia Science Daily It is only possible, by using appropriate animal model that reproduces relevant pathophysiology, to uncover the process of pathogenesis and to develop therapy. Since the research on abnormalities of bones in TD is progressing with iPS cells at Kyoto ...

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From skin to brain: Stem cells without genetic modification: Study ... Science Daily A discovery, several years in the making, demonstrates that adult skin cells can be converted into neural crest cells (a type of stem cell) without any genetic ... From skin to brain: Stem cells without genetic modification - UB Now ...University at Buffalo Reporter all 2 news articles »

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From skin to brain: Stem cells without genetic modification: Study ... - Science Daily

Electroacupuncture releases stem cells to relieve pain, promote tissue repair, study finds Science Daily "The acupuncture stimulus we're giving these animals has a rapid effect on neuroanatomical pathways that connect the stimulus point in the arm to responsive neurons in the spinal cord and into a region in the brain called the hypothalamus. In turn, the ...

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Three women suffering from a degenerative eye condition were blindedlikely permanentlyin a clinical trial for stem cell therapy, according to a report published Wednesday in the New England Journal of Medicine.

The women, who were all between the ages of 72 and 88, had a common medical condition called age-related macular degeneration, in which cells in the retina begin to die off, resulting in spotty or blurred vision. Researchers suspected stem cells derived from the patient's own body could regenerate some of the cells lost to the disease. So in the clinical trial, which was conducted in 2015, researchers removed some blood and fat from participants' anesthetized abdomens, treated the cells in a standardized way to make them revert to stem cells, then injected into their eyes. They were instructed to use an eyedrops antibiotic for a few days. The three patients had found the trial listed on the government web site clinicaltrials.gov, and had each paid $5,000 for the procedure. The informed consent form listed that blindness was possible as a result of the procedure.

MoreIt's Shockingly Easy To Buy Unregulated Stem Cell Treatments

A few days after the patients received the injected stem cells, the participants ended up in the hospital with vision loss, detached retinas, and hemorrhage. The patients lost vision; subsequent checkups led doctors to conclude that they would likely never regain their sight.

Despite the fact that the participants found the procedure on clinicaltrials.gov, the informed consent forms do not mention that it is in fact a clinical trial. "The patients paid for a procedure that had never been studied in a clinical trial, lacked sufficient safety data, and was performed in both eyes on the same day," the study authors write. Injecting something experimental into both eyes is both not safe and not typical, they continue.

Recently researchers have been testing lots of different medical uses for stem cells, from treating multiple sclerosis to spinal cord injuries. With the passage of the 21st Century Cures Act in December, Congress cleared the way for faster regulatory approval for promising treatments based on stem cells. At least 13 clinical trials were registered to treat AMD alone as of November 2016, the article authors write.

But anecdotes like these bolster those who counsel restraint when it comes to stem cells. "Although numerous stem-cell therapies for medical disorders are being investigated at research institutions with appropriate regulatory oversight, many stem-cell clinics are treating patients with little oversight and with no proof of efficacy," the article authors write.

Jeffrey Goldberg, a professor of ophthalmology at Stanford University and one of the authors of the article, calls this a "call to awareness for patients, physicians and regulatory agencies of the risks of this kind of minimally regulated, patient-funded research," according to a press release.

The post Three Women Blinded In Stem Cell Clinical Trial appeared first on Vocativ.

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3 women blinded in stem cell clinical trial - AOL

Updated March 17, 2017 13:31:00

Queensland researchers have used stem cells to create a beating human heart muscle, as well as heart tissue that is able to repair itself.

Doctors James Hudson and Enzo Porello from the University of Queensland worked with German researchers to create the samples in a laboratory, and will use them to study cardiac biology and diseases.

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

Up until now researchers have had no "living" tissue to study, but now scientists have a viable, functioning heart muscle to work on.

Dr Hudson said it would help them model the cardiovascular disease, screen new drugs and investigate heart repair.

"Immature tissues were found to have the ability to regenerate following injury something that did not occur naturally for adults," he said.

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

"We found that when we injured those tissues in contrast to what happens normally in the heart where you get a 'dead' patch muscle function fully recovered because the cells regenerate.

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

While the researchers have grown samples of beating heart tissue, they are not full size.

Dr Hudson said they were about 1 centimetre long and 1 millimetre wide.

He said about 54,000 Australians had heart attacks each year, with an average of about 23 deaths a day.

"Current pharmaceuticals can help those people in the shorter term, however some of those patients still progress to heart failure," Dr Hudson said.

"The holy grail goal of all this is to come up with new regenerative therapeutics to cure those patients."

The research team hopes to commercialise the technology, which it believes will help save lives.

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

Topics: medical-research, health, diseases-and-disorders, heart-disease, science-and-technology, research, qld, university-of-queensland-4072, australia

First posted March 17, 2017 13:11:06

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Self-repairing heart tissue breakthrough brings hope for cardiac ... - ABC Online

A non-surgical treatment that uses a patients own bone marrow stem cells to treat chest pain or angina improved both symptoms and the length of time treated patients could be physically active, according to recent research.

Angina is chest pain or discomfort caused when the heart does not get enough oxygen-rich blood due to narrowing or blockages in the arteries leading to the heart.

Most studies that have explored stem-cell therapies for angina required surgery to directly inject stem cells into the heart muscle or the heart blood vessels.

We injected a catalyst molecule that caused bone marrow stem cells to enter the patients blood, then harvested them to re-inject into the patient.

This is not considered a surgical procedure, is easy to implement, and allows for repeated administrations, said Hadyanto Lim, Ph.D., study senior author.

Fifteen patients were first injected with a molecule called granulocyte colony stimulating factor (G-CSF) once a day for four days.

G-CSF stimulates stem cells to migrate into the bloodstream from the bone marrow where they reside. Stem cells have the ability to transform into different types of cells.

On the fourth day, three hours after the last G-CSF injection, blood was drawn and stem cells were separated from the blood.

Stem cells were identified by the presence of a protein called CD34 on the cells surface.

Thirty minutes after the cell separation procedure finished, the collected stem cells were injected back into the patient through an IV.

Four weeks after receiving the treatment, patients experienced significantly fewer angina-related symptoms, and they were able to exercise at a higher intensity and for a longer period of time.

Most patients also reported mild muscle pains in their backs or legs, but the pain could be managed with acetaminophen.

When lifestyle changes and drug therapies do not control chest pains and discomfort, patients are often recommended for surgical procedures.

This includes coronary angioplasty in which a small mesh tube is inserted in the narrow heart artery to open it up and coronary artery bypass grafting in which healthy blood vessels are used to shunt blood around the narrowed heart arteries.

However, 20 percent to 30 percent of patients with severe coronary atherosclerosis are not suitable for these interventions.

The studys limitations are the small number of patients and absence of a control group. Because no control group was used, the placebo effect cannot be ruled out, Lim noted.

Although this treatment is currently used to treat some cancers multiple myeloma and lymphoma it will need more investigation before it can be made available to the general public to treat angina, according to Lim.

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Having chest pain? Your own stem cells may help with the treatment - Knowridge Science Report

Seven-month-old Madalayna Ducharme is receivingthe stem celltransplant she urgently needs to save her life, from a donor found in herWindsor home her two-year-old brother Henrik.

But her mother Tamara cautioned Friday that the hardest days start today as specialistsat Torontos Sick Kids hospital closely monitor for the next several weeks how Madalayna responds to her brothers stem cells, needed to halt the terrible effects of malignant infantile osteopetrosis.

Theone-in-200,000 genetic disorder causes bones toget thicker and more dense. She cant lift her head because its too heavy. One of the most devastatingeffects vision loss caused by thickening bones compressing nerves has already happened since her January diagnosis.

People dont get how difficult this still is, Tamara said during a phone interview Friday from Sick Kids. Once the match was found (last week) everyone was so excited. But then there was eight days of chemo, to kill off Madalaynas own stem cells and make room for those from her brother. The chemo was tough on Madalayna, Tamara said.

And that isnt even the most difficult part. We keep being told its going to get a lot harder before it gets better.

She said doctors will monitor her for signs of rejection for the next 14-27 days in Toronto. Theres a risk of graft versus host disease, which can happen if Henriks donated bone marrow thinks Madalaynas body is foreign and attacks her.

When Tamarawas interviewed on Friday, she and husband Charles were waiting while Henrik was donating his bone marrow a 3-hour procedure called harvesting. Madalayna was on Tamaras lap, waiting for the procedure that involves transfusing the bone marrow into her system, much like a blood transfusion.

The Ducharme family at their home in Windsors Riverside area on Jan. 18, 2017. From left: Henrik, Tamara, Charles, and warrior princess Madalayna. Nick Brancaccio / Windsor Star

Because hes only two, Henrik only understands that hes helping his sister, Tamara said.He was very willing, she said, because he knows she is very sick.

The family went public in January to plead for people to get swabbed tested to see it theyre a match and to register on the international bone marrow registry. About 1,500 volunteered, said Tamara.

Its phenomenal, she said of the response. Its very uplifting, it makes you feel really great that people are behind us. She said social media posts about Madalaynas progressare followed by 7,000-15,000 people.

Shes got a lot of prayers and thoughts behind her, so shes going to be OK.

Tamara said Madalaynas eyes have been affected by the disease, but doctors arent yet 100 per cent sure if shes entirely lost her eyesight a permanent effect from the disease.

Madalayna appeared perfectly healthy when she was born, but at two months, theirfamily doctor noticed herfontanel the soft spot in a babys skull was enlarged. It was the start of a long list of symptoms such as spitting up, seizures, spots on the liver and abnormal findings from blood work, ultrasounds and other tests. The definitive diagnosis came in January.

When the Ducharmes made their public appeal for people to get swabbed, the situation was an emergency due to the possible arrival of terrible complications, including lost eyesight and hearing.

Windsor is such a great community, as soon as you put a call out, people are willing to help, theyre always there in abundance, said Joanne Bedard, whose Katelyn Bendard Bone Marrow Associationorganizedlocal bone marrow registrations in Madalaynas name.

About 1,300 people registered with CanadasOne Matchstem cell and marrow registry, not including other donors who were swabbed at regular Canadian Blood Services blood donor clinics or who submitted their swab sample through the mail.

The fact we had that many people who joined the registry, it just offers so much more hope to the other over 800 Canadians who are waiting for a (stem cell) transplant, said Bedard, whose daughterKatelyn died of leukemia in 2005 when she was three, aftera bone marrow donor could not be found.

When they learned last week that Henrik was a match, doctors were initially hesitant to use him because of concerns his genetic makeup was too close to Madalaynas and could therefore share some of the diseases traits. But they ultimately decided that Henrik was the best option.

Madalayna Ducharme at her family home in Windsors Riverside area on Jan. 18, 2017. The baby warrior princess suffers from the rare disorder of malignant infantile osteopetrosis. Nick Brancaccio / Windsor Star

Friday was Day Zero for Madalayna, and the medical experts will start counting upwards from there as Henriks stem cells start to graft into her system.

Thereare a lot of things that can happen from Day Zero on up until she has accepted this bone marrow, her mother said. So were actually going to be in the roughest days starting today.

A benefit to help the family is planned for April 1 at Parkwood Gospel Temple, 3005 Temple Dr., from 4 p.m. to 8 p.m. Call 226-348-0388 for information about tickets. You can also donate to an account set up at Libro Credit Union. Go to any location and make a deposit to the Warrior Princess account. You can also make an e-transfer towarriorprincesslayna@gmail.com with the password Layna.

bcross@postmedia.com

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Prayers, hopes for Madalayna, as brother donates life-saving stem ... - Windsor Star

I just read a concerning paper about an experimental stem cell treatment for children with autism.

The authors are Himanshu Bansal and colleagues of India. The senior author, Prasad S Koka, is the Editor-in-Chief of the Journal of Stem Cells where the paper appeared, which raises questions about whether the manuscript received a thorough peer review. Koka is actually an author on all five of the research papers published in that issue of the journal. But thats a minor issue compared to the content of the paper.

Bansal et al. describe a procedure in which they extracted fluid from the bone marrow of each child. This fluid (bone marrow aspirate) was treated in the laboratory to purify the stem cells within, and then injected into the childs spinal canal. The whole operation took place under general anaesthesia. 10 autistic children aged 4-12 were treated.

I found this pretty shocking. An invasive procedure involving general anaesthesia should only be performed if its medically justified especially in children as young as 4! Bansal et al. provide no scientific explanation for why they thought this treatment was suitable for these patients. They vaguely name immunological and neural dysregulation believed to underlie autism as the target of the cells.

For what its worth, the results showed a slight improvement in autism symptoms after the treatment. However, there was no control group, so placebo effects are likely, and were told that the patients were also given speech therapy, occupational therapy and psychological intervention which might account for the benefits.

So who gave the green light to this project? Well, remarkably, Bansal et al.s paper contains no information about which ethics committee reviewed and approved the study. I dont know about the laws in India, but in the UK or the USA, conducting even the most benign research without the proper ethical approval is serious misconduct. Most journals absolutely wont publish medical research without an ethics statement.

The paper also contains no mention of conflicts of interest another thing that most medical journals require. I believe that financial conflicts of interest are likely to exist in this case because Bansal gives his affiliations as Mother Cell, his own private venture, and RegennMed, who sell various stem cell treatments.

Overall, to say that this paper is ethically questionable is an understatement, and it would have been rejected by any real journal.

This isnt Dr Himanshu Bansals first foray into the amazing world of dodgy stem-cells. He briefly made headlines around the globe last year when he announced his ReAnima project to bring a brain dead woman back to life (with stem cells). Indian authorities eventually blocked his resurrection attempt. Theres some more interesting dirt on Bansal on this forum.

This is also not the worlds first stem cells for autism trial. For example, Duke University launched a $40 million trial in 2014. The treatment in that trial was a blood infusion, so it was pretty non-invasive: no bone marrow, spinal needles, or general anaesthesia. However, critics argue that its pure speculation to think that stem cells would help in autism. Then again, the same could be said about a great many stem cell therapies.

Bansal H, Verma P, Agrawal A, Leon J, Sundell IB, Koka PS. (2016). A Short Study Report on Bone Marrow Aspirate Concentrate Cell Therapy in Ten South Asian Indian Patients with Autism Journal of Stem Cells, 11 (1)

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Unethical Stem Cell Therapy for Autism In India? - Discover Magazine (blog)

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Stem Cell Therapies for Degenerative Disc Disease Clinical Pain Advisor (registration) MSCs derived from bone marrow have been successfully differentiated into cardiopoietic cells and used in treatment of heart failure. Fourth- and fifth-generation techniques use genetically modified MSCs and induced pluripotent stem cells (iPSCs), ...

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3 Women Blinded After Stem Cell Therapy Newser CORRECTS FROM MD ANDERSON HOSPITAL TO MD ANDERSON CANCER CENTER -Senior Clinical Cell Therapy Specialist Megan Raggio prepares stem cells from bone marrow before they are transplanted into sportscaster... (AP Photo/David J. Phillip). These Women Went Blind After A Florida Clinic Injected Fat Cells Into Their EyeballsBuzzFeed News Florida Clinic Blinds Three Patients in Botched 'Clinical Trial'Gizmodo From Hope To Despair: Three Women Blinded By Unproven Stem Cell Therapy [VIDEO]Counsel & Heal The New England Journal of Medicine -The New England Journal of Medicine -The New England Journal of Medicine -Bascom Palmer Eye Institute all 131 news articles »

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3 Women Blinded After Stem Cell Therapy - Newser

I recently donated peripheral blood stem cells (PBSC) to a middle-aged man with myelodysplastic syndrome. This is similar medically to a bone marrow donation (though less painful) and much more involved than a blood donation (which I have done regularly since I was seventeen). I found the whole process fascinating and a testament to the glory of mans mind and modern civilization.

The patient with myelodysplastic syndrome lives in central Europe. His bodys bone marrow was no longer producing healthy functioning blood cellsthat is, red blood cells, white blood cells, and plateletsa deficiency that could have resulted in his bodys loss of ability to fight infections or control bleeding, and possibly leukemia. The cure for his disease involved destroying his defective natural bone marrow and replacing it with someone elsesmine.

Bone marrow compatibility between donor and recipient is more complicated than blood types. He needed a donor whose human leukocyte antigen (HLA) proteins most closely matched his own in order to minimize the chance of graft-versus-host disease. His doctors found my data in the Be the Match Registry, where Im registered as a potential donor, and they judged my HLA proteins to be his best hope.

Eight weeks before the operation would take place, I was notified by phone about the match and the donation process. I was then asked whether I was willing to donate. I said yes (and was given several opportunities later to change my mind). In the following weeks, I provided two sets of blood samples to verify that I was healthy enough to donate and still a good match. I was flown out to the donation facility in Michigan to be examined physically, preview the process, and speak with the doctors and nurses who would collect the donation. My donor representative called me periodically to keep me informed and to verify my continuing consent. She also made the arrangements for collecting the samples, managed my travels, and ensured that my expenses were covered.

Here I am holdingthe final product just prior to its transportation to the recipientin central Europe.

As the donation date drew closer, I received ten shots of Filgrastim, a drug designed to stimulate additional blood stem cell formation, one shot in each arm for five days. This increased my white blood cell count far above normal and forced extra blood stem cells into my bloodstream, thus enabling the technicians to run my blood through an apheresis machine, which separated the phases of blood by density using centripetal acceleration. On the donation day, I sat in a comfy chair with an IV in each arm for four hours as a machine took blood from one arm, separated out the stem cells, and returned the rest of my blood via my other arm. While the process continued throughout the morning, the nurses took a few notes here and there, and, as my arms couldnt bend, fed me lunch (chicken wings from Jets Pizza). Once the machine had collected enough stem cells for the recipient (Im fifteen pounds heavier than he is, so it was easier on my body than it could have been), the IVs were removed, my blood was tested one final time to make sure I was OK to drive home, and I left.

My blood stem cells were then transported by private courier to the patient in central Europe. In preparation for the donation, his entire immune system and blood-producing machinery (bone marrow) had been destroyed using myeloablative chemotherapy in order to eliminate any remaining diseased cells and to suppress any immune response from his body to my replacement tissue. My blood stem cells were injected into his bloodstream by IV and then migrated to his bones to replace his destroyed bone marrow and eventually start producing new red blood cells, white blood cells, and platelets. Essentially, my blood and my immune system are regrowing in his body. With these, he inherits my allergies and infectious disease history, and, if all goes well, my life force for another few decades.

Although the organization through which I donated does not pay for stem cells (because payment is against international registry standards), I was treated well and fully reimbursed for expenses. They paid for flights, a half dozen meals, a private driver at one point, hundreds of miles of my own driving, and my stays at nice hotels.

It is worth noting that the Institute for Justice (IJ) recently sued the U.S. attorney general to legalize bone marrow and stem cell donor compensation.1 As the IJ reports, the Ninth Circuit ruled in our favor, holding that the National Organ Transplant Acts ban on donor compensation does not apply to the most common method for donating marrow. This victory is especially helpful for certain minorities and people with multiracial ancestries who face significantly reduced odds of finding unrelated marrow donors. But direct compensation has been met with strong resistance by the major national and international marrow registry organizations, which also lobbied against IJs efforts in court.2 Currently, compensation for donations is being offered only by smaller organizations.

My motivation for donating cannot be reduced to just one reason, but it certainly was not a sacrifice. My reasons varied in depth and weight, but all were self-interested. I thought the process itself was fascinating. I was able to ask the doctors and nurses unlimited questions and to experience firsthand a medical procedure about which I had no previous knowledge. I enjoyed business-class travel, which, as a college student was a significant treat. Most broadly, I participated in an important aspect of the kind of civil society in which I want to live. I want someone to be willing to donate lifesaving tissue to me or my loved ones, should we need it in the future, and I was happy to donate first. The costs were trivialabout twenty-five hours of volunteered time and some minor discomfort. Overall, the experience was positive and spiritually rewarding.

The option to make a donation of this kind did not even exist a few decades ago. It is a function of many interrelated parts of todays modern, relatively free-market, science-oriented cultures. The establishment and maintenance of an international donor registry requires stable, relatively rights-protecting legal systems that enable long-range and large-scale planning among cooperative strangers. To find matches in a timely manner requires the speed and integrating capacities of computers and the Internet. The medical procedure itself requires the kinds of scientific knowledge and expensive technologies made possible by todays relatively free markets. The ability to pay for such a procedure requires substantial personal wealth, which more people have today than ever before. I am exceedingly grateful to live in our rich, science-oriented, relatively capitalist civilization at the time that I do. And I hope the recipient of my donation is able to enjoy many years more of living and loving life as I do.

Related:

Endnotes

1. Bone MarrowNOTA Challenge, Institute for Justice, http://ij.org/case/bonemarrow/.

2. Coalition Says PBSC Donor Compensation Poses Health Risks to Patients and Donors, Be the Match, February 2, 2012, https://bethematch.org/news/news-releases/coalition-says-pbsc-donor-compensation-poses-health-risks-to-patients-and-donors/.

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My Non-Sacrificial Donation of Stem Cells to Save a Life - The Objective Standard

Buffalo, NY (Scicasts) 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 Dr. Stelios T. Andreadis, 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 reprogramming 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 Dr. Gabriella Popescu, professor in the Department of Biochemistry in the Jacobs School of Medicine and Biomedical Sciences at UB; Dr. Song Liu, 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 Dr. Marianne Bronner, 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.

Article adapted from a University at Buffalo news release.

Publication: Reprogramming Postnatal Human Epidermal Keratinocytes Toward Functional Neural Crest Fates. Stelios T. Andreadis et al. Stem Cells (2017): Click here to view.

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Study Yields Neural Crest Cells from Adult Skin Cells Without Genetic Modification - Scicasts (press release) (blog)

Aired 3/16/17 on KPBS News.

A research team led by UC San Diego scientists have created a lab-grown model of the anorexic brain using stem cells derived from patients with the eating disorder.

Researchers led by San Diego scientists have created a lab-grown model of the anorexic brain using stem cells derived from patients with the eating disorder. They say the results provide further evidence for understanding anorexia as largely genetically based, rather than primarily as a socially conditioned behavior.

"There's a stigma regarding eating disorders that it's something social," said UC San Diego researcher Alysson Muotri. "But in fact, our results point to a strong genetic factor. And moreover, it suggests there's a specific pathway in the brain that is altered."

For the study published Tuesday in the journal Translational Psychiatry, Muotri and his colleagues took skin cells from seven anorexia patients and then converted them into stem cells in the lab. They then coaxed those stem cells into brain cells, providing scientists with a new model for studying the eating disorder.

Muotri, who has developed similar models for other diseases, said the "disease-in-a-dish" approach is great for studying neurological disorders. Scientists wanting to study these diseases "can't just open the skull and look through the brain cells," he said.

The researchers compared anorexic brain models with other models built from cells taken from four non-anorexic people, most of them relatives of the anorexic patients. The researchers found a difference in the TACR1 gene between the two groups.

Muotri admits the number of patients studied was small, but says these results support "the idea that anorexia has a fundamental biological basis on the perception of fat in the body."

Anorexia experts not involved in the study told KPBS this is another step toward understanding the underlying biology of a misunderstood and often deadly disease.

Walter Kaye, director of the UCSD Eating Disorder Research and Treatment Program, said in an email to KPBS that the findings establish an interesting link between anorexia and a genetic pathway known to play a role in anxiety and fat metabolism.

"This may be a very important clue to understanding puzzling symptoms in anorexia nervosa, such as why food is often associated with anxiety, and why patients see themselves as fat and tend to avoid fat-containing foods," Kaye wrote.

Christina Wierenga, co-director of the eating disorder research program at UCSD, wrote in an email to KPBS, "Although the sample size is small, this elegant study is the first of its kind to examine gene expression in neurons derived from individuals with anorexia and sheds new light on possible causes of anorexia. Of course, replication in larger samples is needed."

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How Stem Cells Could Help Scientists Study Eating Disorders - KPBS

Masayo Takahashi (second from left) treated macular degeneration with retinal tissue grown from iPS cells.

Kyodo News/Contributor/getty images

By Dennis NormileMar. 15, 2017 , 5:00 PM

Its official: The first use of induced pluripotent stem (iPS) cells in a human has proved safe, if not clearly effective. Japanese researchers reported in this weeks issue of The New England Journal of Medicine (NEJM) that using the cells to replace eye tissue damaged by age-related macular degeneration (AMD) did not improve a patients vision, but did halt disease progression. They had described the outcome at conferences, but publication of the details is an encouraging milestone for other groups gearing up to treat diseased or damaged organs with the versatile replacement cells, which are derived from mature tissues.

This initial success is pretty momentous, says Alan Trounson, a stem cell scientist at the Hudson Institute of Medical Research in Melbourne, Australia. But the broader picture for iPS therapies is mixed, as researchers have retreated from their initial hopes of creating custommade stem cells from each patients tissue. That strategy might have ensured that recipients immune systems would accept the new cells. But it proved too slow and expensive, says Shinya Yamanaka of Kyoto University in Japan, who first discovered how to create iPS cells and is a co-author of the NEJM paper. He and others are now developing banks of premade donor cells. Using stocks of cells, we can proceed much more quickly and cost effectively, he says.

Even so, clinical work is progressing more quickly than I had expected, says Yamanaka, who did his groundbreaking work just a decade ago. His collaborator on this trial, Masayo Takahashi of the RIKEN Center for Developmental Biology in Kobe, Japan, had a head start. An ophthalmologist, Takahashi was familiar with the ravages of AMD, a condition that progressively damages the macula, the central part of the retina, and is the leading cause of blindness in the elderly.

Takahashi started investigating treatments for AMD in 2000, a time when the only cells capable of developing into all the tissues of the body had to be extracted from embryos. But she was stymied by immune reactions to these embryonic stem (ES) cells. When Yamanaka announced that he could induce mature, or somatic cells, to return to an ES celllike state, Takahashi quickly changed course to develop a treatment based on iPS cells.

Her team finally operated on the first patient, a 77-year-old Japanese woman with late-stage AMD, in September 2014. They took a sample of her own skin cells, derived iPS cells, and differentiated them into the kind of retinal cells destroyed by the disease. A surgeon then slipped a small sheet of the cells into the retina of her right eye.

An operation on a second patient was called off because a number of minor genetic mutations had crept into his iPS cells during processing, and uncontrolled growthcancerhas been a worry with such cells. These changes do not directly induce cancer, but we wanted to make safety the first priority, Yamanaka says. Also, Takahashi says, AMD drugs had stabilized the patients condition so there was no urgency in subjecting him to the risks of surgery, which include hemorrhaging and retinal damage.

Immediately after surgery the first patient reported her eyesight was brighter. Takahashi says the surgery halted further deterioration of her eye, even without the drug injections still being used to treat her other eye, and there were no signs of rejection of the graft as of last December.

Clinical work is progressing much more quickly than I expected.

The result is a proof of principle that iPS cellbased therapy is feasible, says Kapil Bharti, a molecular cell biologist at the U.S. National Institutes of Healths National Eye Institute in Bethesda, Maryland, who is also developing iPS cells for treating AMD. Takahashi says once her team gains more experience with the technique they will extend it to patients with earlier-stage AMD in an effort to preserve vision.

Last month, Takahashi won approval to try the procedure on another five patients with late-stage AMD. But this time, instead of using iPS cells derived from each patient, the team will draw on banked cells from a single donor. It takes time to create iPS cells, and a lot of time for the safety evaluation, Yamanaka says. It is also costly, at nearly $900,000 to develop and test the iPS cells for the first trial, Takahashi adds.

Using donor cells to create the iPS cells will make it more difficult to ensure immune compatibility. But Yamanaka says that donor iPS cells can be matched to patients based on human leukocyte antigen (HLA) haplotypessets of cell-surface proteins that regulate immune reactions. HLA-matched cells should require only small doses of immunosuppressive drugs to prevent rejection, Takahashi saysand perhaps none at all for transplantation into the immune-privileged eye.

Kyoto Universitys Center for iPS Cell Research and Application, which Yamanaka heads, has been developing an iPS cell bank. Just 75 iPS cell lines will cover 80% of the Japanese population through HLA matching, he says. Trounson, a past president of the California Institute for Regenerative Medicine, a stem cell funding agency, says banked iPS cells have advantages. Donor iPS cells may be safer than cells derived from older patients, whose somatic cells may harbor mutations. And Jordan Lancaster, a physiologist at the University of Arizona in Tucson, likes the speed of the approach. He is devising patches for heart failure patients based on iPS-derived myocardial cells that will be premanufactured, cryopreserved, and ready to use at a moments notice.

Patient-specific iPS cells will still have clinical uses. For one thing, Bharti says it will be difficult for cell banks to cover all HLA haplotypes. And a patients own iPS cells could be used to screen for adverse drug reactions, says Min-Han Tan, an oncologist at Singapores Institute of Bioengineering and Nanotechnology, who recently published a report on the approach.

Other human trials are not far behind. Yamanaka says his Kyoto University colleague Jun Takahashi (Masayo Takahashis husband) will launch trials of iPS-derived cells to treat Parkinsons disease within 2 years. Bharti hopes to start human trials of iPS cells for a different type of macular degeneration next year. And as techniques for making and growing iPS cells improve, researchers can contemplate treatments requiring not just 100,000 cells or sothe number in Takahashis retinal sheetsbut millions, as in Lancasters heart patches.

As clinical use approaches, Takahashi cautions that researchers need to keep public expectations realistic. For now, iPS treatments may help but wont fully reverse disease, she says. Regenerative medicine is not going to cure patients in the way they hope.

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Cutting-edge stem cell therapy proves safe, but will it ever be effective? - Science Magazine

The new report says the three women, in their 70s and 80s, paid $5,000 to be treated in 2015 for age-related macular degeneration. Participants can also report their concerns to the Office for Human Research Protections within the U.S. Department of Health and Human Services.

The "devastating outcomes" experienced by the women raise the "need for oversight of such clinics and for the education of patients by physicians and regulatory bodies", the paper said.

The women all suffered detached retinas, vision loss, and hemorrhages in their eyes.

"We don't mean to say all stem cell clinical studies are risky", coauthor Dr. Thomas Albini of the University of Miami told Reuters Health in a telephone interview.

Paul Knoepfler, a stem-cell scientist at the University of California at Davis who is a frequent critic of the clinics, said he didn't understand why the FDA and the NIH have not moved more aggressively to ensure patient safety. They sought treatment at a Florida clinic that had announced a study to treat the condition on clinicaltrials.gov, a federal database of research studies. Two out of the three patients found the trial through the website, which doesn't fully vet trials for scientific soundness. "Platelet count increased to 1.01m3 following the treatment and there were remarkable improvements in other symptoms", said Geeta Shroff, Stem Cell Specialist, Director, Nutech Mediworld. Stem cell clinics have cropped up all over the United States in recent years and are operating in a self-perceived regulatory loophole. Stem cells were then extracted from the fat and injected into their eyes. Albini says the complications could have come from injecting a contaminant into the eye, or from the fact that the stem cells may have turned into myofibroblasts after the injections, which are cells associated with scarring.

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

Legitimate medical research seldom requires patients to pay and, in the case of eye treatments, only one eye is treated at a time so doctors can gauge its effectiveness, the Kuriyan team said.

Although the women had moderate vision loss prior to the stem cell treatments, a year later their vision ranged from total blindness to 20/200, which is considered legally blind.

And even if the interventions were done well, they say, there is no evidence that they could have restored the patients' vision. They first cultivate stem cells to form the retinal pigmented epithelial cells that are needed to restore a damaged retina.

Shoddy stem cell preparation may have led to some of the complications, said the study authors.

The episode, described Wednesday in an article in the New England Journal of Medicine, represents one of the most egregious examples of patient injury involving a stem-cell clinic. The company also noted that it does not now treat eye patients.

The paper also mentions that the women believed that they were taking part in a clinical trial because they were aware of the clinic's work on the ClinicalTrials.gov website run by the U.S. National Library of Medicine. In other words, the company claims the study was stopped before patients were enrolled. In fact, doctors have done bone marrow transplant, a procedure where stem cell transplantation is performed.

"There's this perception that there are all these stem cell therapies out there that are close to clinical application that. are being held back by regulators and if they just step back, there would be all these treatments", he said. However, it can be hard for patients to distinguish between trials that are legitimate, and those that are not, the authors wrote.

"There's no excuse for not designing a trial properly and basing it on preclinical research", added study Jeffrey Goldberg, also a study author, of Stanford University's School of Medicine.

Researchers from the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg and an global team have now identified an ingenious mechanism by which the body orchestrates the regeneration of red and white blood cells from progenitor cells.

See if a trial is affiliated with an academic medical center - that's a good sign it is legitimate, they say.

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3 women blinded after receiving stem cell therapy for macular degeneration - ClickLancashire

Luxembourg (Scicasts) Stem cells are unspecialized 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. The LCSB team has published its results in the scientific journal PLOS Biology.

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.

Article adapted from a University of Luxembourg news release.

Publication: Cell Fate Decision as High-Dimensional Critical State Transition. Mitra Mojtahedi et al. PLoS Biol. (2016): Click here to view.

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Team Deciphers How the Body Controls Stem Cells - Scicasts (press release) (blog)

March 17, 2017 Left: Cross-sectional view of the cerebrum in normal ferret. Neurons are localized in the cerebral cortex, the surface layer of the cerebrum. Since the surface of the cerebrum has folds (gyri), the layer containing neurons winds on its way. Right: Cross-sectional view of the cerebrum in TD ferret. Clusters of neurons (indicated by arrows) are found deep in the cerebrum, which are not detected in the cerebrum of normal ferret. They are called 'periventricular nodular heterotopia,' PNH. In addition, in the surface layer, a larger number of smaller folds (gyri) are seen than normal (indicated by asterisks). They are called polymicrogryri. Credit: Kanazawa University

Thanatophoric dysplasia (TD) is an intractable disease causing abnormalities of bones and the brain. In a recent study of ferrets, which have brains similar to those of humans, researchers using a newly developed technique discovered that neuronal translocation along radial glial fibers to the cerebral cortex during fetal brain development is aberrant, suggesting the cause underlying TD.

In TD cases, the limb and rib bones are shorter than normal, and brain abnormalities manifest, including polymicrogyria and periventricular nodular heterotopia. Previous research has determined that a gene, fibroblast growth factor receptor 3 (FGFR3), is responsible. However, as a result of TD rarity and the difficulty of obtaining brain samples from human patients, the pathophysiology of TD is largely unknown, and effective therapy has not been established.

The present research team of Kanazawa University generated an animal model of TD using ferrets that reproduces the brain abnormalities found in human TD patients. By using this animal model, the team elucidated the formation process of polymicrogyria, one of the abnormalities found in the TD brain. The team has also investigated the formation process of PNH, the other brain abnormality found in human TD patients.

First, PNH was analyzed in terms of composing cell types to reveal that a large number of neurons but few glial cell exist in PNH. In a healthy brain, neurons are found in the cerebral cortex near the brain surface. The researchers believe that during fetal brain development, PNH formation might be induced by the inability of neurons to translocate themselves to the cerebral cortex. The researchers found that the spatial arrangement of radial glial cells was distorted; radial glial fibers are believed to serve as the "track" for neurons to translocate themselves. Thus, the distortion of radial glial fibers seems to be a reason for aberrant localization of neurons.

Research on abnormalities of bones in TD is progressing with iPS cells at Kyoto University, and it is expected that the whole aspect of TD with brain and bone abnormalities would be elucidated and that the therapeutic methods would be developed. The present study on PNH was only possible using the experimental technique for ferrets developed by the research team. This animal model technique could also contribute to studies of other neurological diseases that have been difficult to investigate with conventional model animals.

Explore further: Researchers discover a gene's key role in building the developing brain's scaffolding

More information: Naoyuki Matsumoto et al, Pathophysiological analyses of periventricular nodular heterotopia using gyrencephalic mammals, Human Molecular Genetics (2017). DOI: 10.1093/hmg/ddx038

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Researchers develop new animal model to study rare brain disease - Medical Xpress

Three women suffering from a degenerative eye condition were blindedlikely permanentlyin a clinical trial for stem cell therapy, according to a report published Wednesday in the New England Journal of Medicine.

The women, who were all between the ages of 72 and 88, had a common medical condition called age-related macular degeneration, in which cells in the retina begin to die off, resulting in spotty or blurred vision. Researchers suspected stem cells derived from the patients own body could regenerate some of the cells lost to the disease. So in the clinical trial, which was conducted in 2015, researchers removed some blood and fat from participants anesthetized abdomens, treated the cells in a standardized way to make them revert to stem cells, then injected into their eyes. They were instructed to use an eyedrops antibiotic for a few days. The three patients had found the trial listed on the government web site clinicaltrials.gov, and had each paid $5,000 for the procedure. The informed consent form listed that blindness was possible as a result of the procedure.

A few days after the patients received the injected stem cells, the participants ended up in the hospital with vision loss, detached retinas, and hemorrhage. The patients lost vision; subsequent checkups led doctors to conclude that they would likely never regain their sight.

Despite the fact that the participants found the procedure on clinicaltrials.gov, the informed consent forms do not mention that it is in fact a clinical trial. The patients paid for a procedure that had never been studied in a clinical trial, lacked sufficient safety data, and was performed in both eyes on the same day, the study authors write. Injecting something experimental into both eyes is both not safe and not typical, they continue.

Recently researchers have been testing lots of different medical uses for stem cells, from treating multiple sclerosis to spinal cord injuries. With the passage of the 21st Century Cures Act in December, Congress cleared the way for faster regulatory approval for promising treatments based on stem cells. At least 13 clinical trials were registered to treat AMD alone as of November 2016, the article authors write.

But anecdotes like these bolster those who counsel restraint when it comes to stem cells. Although numerous stem-cell therapies for medical disorders are being investigated at research institutions with appropriate regulatory oversight, many stem-cell clinics are treating patients with little oversight and with no proof of efficacy, the article authors write.

Jeffrey Goldberg, a professor of ophthalmology at Stanford University and one of the authors of the article, calls this a call to awareness for patients, physicians and regulatory agencies of the risks of this kind of minimally regulated, patient-funded research, according to a press release.

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Three Women Blinded In Stem Cell Clinical Trial - Vocativ

By Isaac GuererroStaff writer

Xue-Jun Li spends her days studying motor neurons, the cells that send signals from the brain to the body's voluntary muscles.

Motor neuron diseases are degenerative, which means that the muscles don't stop working all at once. When the motor neurons begin to fail, one slowly loses control of the arms and legs, the ability to swallow and, eventually, to breathe.

Scientists know very little about the human nervous system and what causes the motor neurons to stop functioning. Li has published more than 37 peer-reviewed manuscripts and has developed human stem cell models for spastic paraplegias and spinal muscular atrophy, which is the leading genetic cause of death for infants.

Li joined the University of Illinois College of Medicine at Rockford as an associate professor in the Biomedical Sciences Department last May. Her research is supported by the National Institute of Health and ALS Association, among others.

I love the satisfaction of new discoveries, new ideas you get from working in the lab, the interaction with students, she said. But any breakthrough you make is a collaboration.

Her stem cell research is concerned with, among other things, an attempt to better understand microtubule defects that disrupt signals from the brain to motor neurons along the spinal cord. Mitochondrial defects the mitochondria are the energy factories of the cells are another focus.

This fall, Li will teach a class that's a first for the university: stem cells and regenerative engineering.

Isaac Guerrero: 815-987-1361; iguerrero@rrstar.com;@isaac_rrs

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Transform 815: Xue Jun-Li's stem cell research in Rockford sheds light on motor neuron diseases - Rockford Register Star

BRUSSELS 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)

LONDON A French biotech firm is hoping to gain approval within months for a nuclear medicine targeting the type of cancer that killed Steve Jobs.

NEW YORK Developers of an experimental blood test for autism say it can detect the condition in more than 96 percent of cases and do so across a broad spectrum of patients, potentially allowing for earlier diagnosis, according to a study released on Thursday.

(Reuters Health) - Getting too little sleep in early childhood is linked to cognitive and behavioral problems years later, a U.S. study suggests.

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