Scientists Find New Way to Up Safety Factor of Stem Cell Therapy by Causing Contaminated Cells to Purge Themselves

Reporting in the October issue of STEM CELLS Translational Medicine, researchers at the Mayo Clinic, Rochester, Minn., think they might have found a low-cost, highly-effective way to detect and then purge at-risk cells during an early stage in the differentiation process.

Durham, NC (PRWEB) September 27, 2012

Now, researchers at the Mayo Clinic, Rochester, Minn., think they might have found an answer. Reporting in the October issue of STEM CELLS Translational Medicine, they detail a low-cost, highly-effective way to detect and then purge at-risk cells during an early stage in the differentiation process.

Strategies to improve the safety of stem cell therapy have generally focused on separating or depleting damaged cells after the cells have differentiated. However, while this method was able to diminish the number of tumors formed as well as significantly reduce their size, the technical burdens and cost of specialized reagents and equipment needed to do so remain a challenge for widespread clinical applications, says lead investigator Timothy J. Nelson, M.D., Ph.D. He directs the cell biology group within the clinics Regenerative Strategies team.

Instead, the Mayo team turned to a relatively simple protocol that involves pre-treating cultured stem cells with a genotoxin an agent that sniffs out gene mutations or chromosomes changes in contaminated cells and kills them after first priming the cells through the up-regulation of Puma protein, which can be activated to send a series of signals leading to cell suicide. They tested their theory using stem cells taken from a mouse model.

The results showed that not only did the contaminated cells die off, At the same time, it didnt affect the remaining healthy cells capability to differentiate nor did it have any negative consequence on their genomic stability, Nelson says. And it worked on stem cells derived from both natural and bioengineered sources.

This novel strategy, based on innate mechanisms of pluripotent stem cells, is primed for high-throughput and cost-effective clinical translation.

The potential for tumor formation has been a significant drawback to therapeutic use of certain cell populations, said Anthony Atala, M.D., Editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. The strategy outlined in this manuscript shows promise for avoiding the risk of uncontrolled cell growth upon transplantation.

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The full article, Apoptotic susceptibility to DNA damage of pluripotent stem cells facilitates pharmacologic purging of teratoma risk, can be accessed at: http://www.StemCellsTM.com.

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Scientists Find New Way to Up Safety Factor of Stem Cell Therapy by Causing Contaminated Cells to Purge Themselves

New Procedure Saves Dogs Lives

GREEN BAY, WI--A breakthrough in veterinary medicine In Green Bay. Two dogs recover amazingly well after receiving stem cell transplants at Packerland Veterinary Center two months ago. They are the first vet clinic in Wisconsin to perform the procedure.

It's a story that gives hope to pet owners all over the country. Stem cells are taken out of the dog's fatty tissue, harvested, then injected into problem areas leaving the dogs completely healed.

"We couldn't take him on walks. He just laid around a lot," said German Shepherd, DeNiro's owner, Keith Noskowiak.

"We'd hear whimpering overnight. She'd take a few steps and she would sit down," said Luther Kortbein, Shadow's owner, another German Shepherd.

But now the dogs have a whole new life. Until two months ago. DeNiro suffered from severe arthritis.

Shadow. suffered from hip dysplasia. The owners were at their wits end. DeNiro's thought he may even have to put his beloved German Shepherd down.

"We felt we had a decision to make with his quality of life and being in pain we didn't want him to be in pain," said Noskowiak.

Shadow's owner was willing to try anything to cure her.

"Whatever the cost needed to get this done we were willing to do," said Kortbein.

Then Packerland Veterinary Center offered them stem cell therapy. The dog's own stem cells are extracted, then injected back into the bloodstream joints.

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New Procedure Saves Dogs Lives

Could this stem cell cure for wrinkles end the endless hunt for the perfect skin cream?

British firm is trialling new method by injecting patient's own stem cells to restore skin's youthful elasticity

By Tamara Cohen

PUBLISHED: 10:40 EST, 9 September 2012 | UPDATED: 02:12 EST, 10 September 2012

Scientists will begin clinical trials in 12 months, using stem cells harvested from a blood sample from the patients

Scientists are working on a new weapon in the war against wrinkles.

There are not many things women have not tried in the quest for a youthful complexion from lotions and potions to Botox and cosmetic surgery.

But a British firm is trialling a new method which involves injecting the patients own stem cells to restore skins youthful elasticity.

Researchers believe they will spur the growth of new skin cells, called fibroblasts, which make the elastic ingredient collagen which is produced in large quantities when we are young, but declines as we age.

The company Pharmacells, based in Glasgow, plan to begin clinical trials in 12 months, using stem cells harvested from a blood sample from the patients.

They believe the procedure could be commercially available in just three years, potentially revolutionising the market for anti-ageing treatments.

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Could this stem cell cure for wrinkles end the endless hunt for the perfect skin cream?

State stem cell research funding agency awards $37.3 million to aid UC Irvine efforts

Public release date: 6-Sep-2012 [ | E-mail | Share ]

Contact: Tom Vasich tmvasich@uci.edu 949-824-6455 University of California - Irvine

Irvine, Calif., Sept. 6, 2012 Efforts to begin human clinical trials using stem cells to treat Alzheimer's disease and retinitis pigmentosa received a $37.3 million boost from the California Institute for Regenerative Medicine during its most recent round of funding on Sept. 5.

UC Irvine scientists will be part of two research teams garnering CIRM Disease Team Therapy Development Awards, which are designed to accelerate collaborative translational research leading to human clinical trials. In one, Dr. Henry Klassen, an associate professor of ophthalmology in UC Irvine's Sue & Bill Gross Stem Cell Research Center, and his collaborators at UC Santa Barbara and Cedars-Sinai Medical Center, received $17.3 million to cultivate therapeutically potent retinal progenitor stem cells to treat the blinding effects of retinitis pigmentosa.

In the other, StemCells, Inc. in Newark, Calif., received $20 million and will collaborate with Frank LaFerla and Mathew Blurton-Jones neurobiologists with the stem cell research center and the Institute for Memory Impairments and Neurological Disorders (UCI MIND) to advance research using the company's proprietary purified human neural stem cells to improve memory in people with Alzheimer's disease.

"CIRM's support for UC Irvine's efforts to advance stem cell-based treatments for a variety of diseases is extremely gratifying," said Peter Donovan, director of the Sue & Bill Gross Stem Cell Research Center. "Henry's work on retinitis pigmentosa and Frank and Mathew's on Alzheimer's disease hold great promise, and we are delighted that they have the support to see their work move toward the clinic."

Klassen's objective is to introduce stem cells that rescue and reactivate damaged and dying photoreceptor rods and cones, thus reversing the course of RP even at relatively advanced stages. The current CIRM funding will allow Klassen and his collaborators to grow these cells under conditions ensuring that pharmaceutical standards are met. The resulting cells will be tested in animals for safety and to make certain that they are therapeutically potent. Then the team will seek FDA approval for the use of these cells in early clinical trials, in which a small number of patients with severe RP will be injected with cells in their worse-seeing eye and followed clinically for a specified period of time to determine the safety and effectiveness of the treatment.

"We believe it's possible to rejuvenate a clinically significant number of cones in the degenerating retina," said Klassen, whose work also has received long-standing support from the Discovery Eye Foundation. "Our methods have been validated, and I'm optimistic that stem cell-based treatments can help restore fading vision in people with eye diseases."

The CIRM award will further LaFerla and Blurton-Jones's efforts with StemCells, Inc. to understand how human neural stem cells can treat Alzheimer's disease, the leading cause of dementia in the U.S. Earlier this year, the researchers reported findings showing that neural stem cells restored memory and enhanced synaptic function in two animal models relevant to Alzheimer's disease, possibly by providing growth factors that protect neurons from degeneration. With these studies establishing proof of concept, the team intends to conduct further animal studies necessary to seek FDA approval to start testing this therapeutic approach in human patients.

"Our goal is to research ways to make memories last a lifetime, and we're excited to investigate the potential efficacy of stem cells for Alzheimer's disease," said LaFerla, the UCI MIND director and Chancellor's Professor and chair of neurobiology & behavior.

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State stem cell research funding agency awards $37.3 million to aid UC Irvine efforts

Brain Cells Derived From Skin Cells For Huntington's Research

Editor's Choice Main Category: Huntingtons Disease Also Included In: Stem Cell Research;Neurology / Neuroscience Article Date: 29 Jun 2012 - 14:00 PDT

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At present, there is no cure for the disease and no treatments are available. These findings open up the possibility of testing treatments for the deadly disorder in a petri dish.

The study is the work of a Huntington's Disease iPSC Consortium, including researchers from the Johns Hopkins University School of Medicine in Baltimore, Cedars-Sinai Medical Center in Los Angeles and the University of California, Irvine, and six other groups.

Huntington's disease is an inherited, deadly neurodegenerative disorder. The onset of HD generally occurs during midlife, although it can also strike in childhood - as in the patient who donated the material for the cells generated in this study. The disease causes jerky, twitch-like movements, lack of muscle control, psychiatric disorders and dementia, and ultimately death.

Christopher A. Ross, M.D., Ph.D., a professor of psychiatry and behavioral sciences, neurology, pharmacology and neuroscience at the Johns Hopkins University School of Medicine and one of the lead researchers of the study, explained:

The team are currently testing small molecules for the ability to block HP iPSC degeneration. According to the researchers, these molecules could potentially be developed into new drugs for Huntington's disease.

Furthermore, the teams ability to create "HD in a dish" may also have implications for similar research in other diseases such as Parkinson's and Alzheimer's.

In the study, the team took a skin biopsy from a 7-year-old patient with very early onset of severe HD. In the laboratory of Hongjun Song, Ph.D., a professor at Johns Hopkins' Institute for Cell Engineering, the skin cells were grown in culture and then created into pluripotent stem cells. In addition, a second cell line was created in the same way in Dr. Ross's lab from an individuals without HD.Simultaneously, other HD and control iPS cell lines were generated as part of the NINDS funded HD iPS cell consortium.

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Brain Cells Derived From Skin Cells For Huntington's Research

Skin Cells Create Stem Cells In Huntington Disease Study

June 29, 2012

Connie K. Ho for redOrbit.com Your Universe Online

In 1993, the autosomal dominant gene mutation responsible for Huntingtons Disease (HD) was discovered. However, no treatments are known to slow its progression. New research may pave the way to better understanding of the disease. Researchers at Johns Hopkins recently announced that they were able to produce stem cells from skin cells from a person who had severe, early-onset form of HD; the cells were then changed into neurons that degenerated like the cells affected by HD.

The research was recently published in the journal Cell Stem Cell. The investigators worked with an international consortium in creating HD in a dish. The group was made up of scientists from Johns Hopkins University School of Medicine, Cedars-Sinai Medical Center, the University of California at Irvine, as well as six other groups. The team looked at many other HD cell lines and control cell lines to verify that the results were consistent and reproducible in other labs. The investigators believe that the findings allow them to better understand and eliminate cells in people in with HD. They hope to study the effects of possible drug treatments on cells that would be otherwise found deep in the brain.

Having these cells will allow us to screen for therapeutics in a way we havent been able to before in Huntingtons disease, remarked lead researcher Dr. Christopher A. Ross, a professor of psychiatry and behavioral sciences, neurology, pharmacology and neuroscience at the Johns Hopkins University School of Medicine, in a prepared statement. For the first time, we will be able to study how drugs work on human HD neurons and hopefully take those findings directly to the clinic.

The team of researchers is studying small molecules for the ability to block HD iPSC degeneration to see if they can be developed into new drugs for HD. As well, the ability to produce from stem cells the same neurons found in HD may have effects for similar research in other neurodegenerative diseases like Alzheimers and Parkinsons. In the experiment, Ross took a skin biopsy from a patient with very early onset HD. The patient was seven years old at the time, with a severe form of disease and a mutation that caused it. By using cells from a patient who had quickly progressing HD, Ross team were able to mimic HD in a way that could be used by patients who had different forms of HD.

The skin cells were grown in culture and reprogrammed to induce stem cells that were pluripotent. Then, another cell line was created in the same way from someone who didnt have HD. The other HD and control iPS cells were produced as part of the NINDS funded HD iPS cell consortium. Investigators from Johns Hopkins and the other consortium labs changed the cells into typical neurons and then into medium spiny neurons. The process took a total of three months and the scientists found the medium spiny neurons from the HD cells acted how the medium spiny neurons form an HD patient would. The cells demonstrated quick degeneration when cultured in the lab with a basic culture medium that didnt include extensive supporting nutrients. On the other hand, control cell lines didnt demonstrate neuronal degeneration.

These HD cells acted just as we were hoping, says Ross, director of the Baltimore Huntingtons Disease Center. A lot of people said, Youll never be able to get a model in a dish of a human neurodegenerative disease like this. Now, we have them where we can really study and manipulate them, and try to cure them of this horrible disease. The fact that we are able to do this at all still amazes us.

Source: Connie K. Ho for redOrbit.com Your Universe Online

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Skin Cells Create Stem Cells In Huntington Disease Study

Turning skin cells into brain cells

Public release date: 28-Jun-2012 [ | E-mail | Share ]

Contact: Stephanie Desmon sdesmon1@jhmi.edu 410-955-8665 Johns Hopkins Medical Institutions

Johns Hopkins researchers, working with an international consortium, say they have generated stem cells from skin cells from a person with a severe, early-onset form of Huntington's disease (HD), and turned them into neurons that degenerate just like those affected by the fatal inherited disorder.

By creating "HD in a dish," the researchers say they have taken a major step forward in efforts to better understand what disables and kills the cells in people with HD, and to test the effects of potential drug therapies on cells that are otherwise locked deep in the brain.

Although the autosomal dominant gene mutation responsible for HD was identified in 1993, there is no cure. No treatments are available even to slow its progression.

The research, published in the journal Cell Stem Cell, is the work of a Huntington's Disease iPSC Consortium, including scientists from the Johns Hopkins University School of Medicine in Baltimore, Cedars-Sinai Medical Center in Los Angeles and the University of California, Irvine, as well as six other groups. The consortium studied several other HD cell lines and control cell lines in order to make sure results were consistent and reproducible in different labs.

The general midlife onset and progressive brain damage of HD are especially cruel, slowly causing jerky, twitch-like movements, lack of muscle control, psychiatric disorders and dementia, and eventually death. In some cases (as in the patient who donated the material for the cells made at Johns Hopkins), the disease can strike earlier, even in childhood.

"Having these cells will allow us to screen for therapeutics in a way we haven't been able to before in Huntington's disease," says Christopher A. Ross, M.D., Ph.D., a professor of psychiatry and behavioral sciences, neurology, pharmacology and neuroscience at the Johns Hopkins University School of Medicine and one of the study's lead researchers. "For the first time, we will be able to study how drugs work on human HD neurons and hopefully take those findings directly to the clinic."

Ross and his team, as well as other collaborators at Johns Hopkins and Emory University, are already testing small molecules for the ability to block HD iPSC degeneration. These small molecules have the potential to be developed into novel drugs for HD.

The ability to generate from stem cells the same neurons found in Huntington's disease may also have implications for similar research in other neurodegenerative diseases such as Alzheimer's and Parkinson's.

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Turning skin cells into brain cells

Stem cell info session held in support of former Guelph boy

GUELPH -- When Sajeed Hussain did not show up for school that Thursday in April, Theresa Darroch didn't think too much of it.

The popular and intelligent student in Darroch's Grade 4 class at Priory Park public school, who had fully participated in gym class just a day earlier, was preparing for a move to Ottawa with his family at the end of the week.

It wasn't until the next day Darroch learned from another student the 10-year-old was in a Toronto hospital after being diagnosed with leukemia.

"It just completely came out of left field," Darroch recalled Saturday. "It was just awful."

Darroch's students have not seen their friend in person since then, as Sajeed's family did move to Ottawa where his father had a new job. But they have kept in touch via Skype, and at Easter Darroch traveled to Ottawa to visit her former student and deliver gifts from students and faculty.

On Saturday, those attending a bone marrow information session organized in Sajeed's honor watched a video, made by the boy's former classmates, wishing him well.

Sajeed has been in and out of hospital in Ottawa and is now one of nearly 1,000 Canadians waiting for a stem cell match.

The Bangladesh Association of Guelph organized the session with Canadian Blood Services in hopes a match for Sajeed could be found, but the purpose soon grew.

"We wanted to help Sajeed, but eventually we thought we could help the wider community because there are more then 900 Canadians who are waiting for a match," said Riadul Mannan, director of communications for the association.

Mannan recalls, too, learning of the boy's illness and being shocked.

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Stem cell info session held in support of former Guelph boy

Columbia Asia Referral Hospital, Yeshwantpur Announces a Comprehensive Bone Marrow Transplant Service

BANGALORE, June 22, 2012 /PRNewswire/ --

Adding an impetus to the already existing image of Bangalore being a healthcare destination of India, Columbia Asia Referral Hospital, Yeshwanthpur (CARHY), announced comprehensive bone marrow transplant (stem cell transplant) service on Thursday. This facility will give hope to many cancer patientsin and around Bangalore as there are very few hospitals in South India providing allogeneic transplant, which involves using stem cellsfrom a donor with a similar genetic makeup.

The bone marrow transplant (BMT) service will have a team of medical experts including clinical hematologist, oncologist, and other qualified doctors from allied specialties like pediatrics, infectious disease specialist and trained nurses for stem cell transplant, state-of-the-art HEPA filtered room, ICU, 24 hrs blood bank services and radiology services for providing comprehensive care during stem cell transplant.

Addressing the media, Dr. Nandakumar Jairam, Chairman and Group Medical Director, Columbia Asia Hospitals,said, "We are happy to announce allogenic bone marrow transplant service at our hospital in Yeshwanthpur, over and above the existing autologous transplant service. This will enhance comprehensive bone marrow transplant treatment delivery; a dire need for the people of Karnataka and neighbouring states. This will also help many international patients who look for such a treatment in India."

"This facility is dedicated to providing end-to-end services including expert counsel from a clinical hematologist and an entire team of doctors and nurses providing the latest in medical advances to those suffering from blood cancer and some non-cancerous conditions affecting thebone marrow," said Dr. Satish, Consultant in Clinical Hematology, Columbia Asia Hospitals.

"Bone marrow transplant, also called hematopoietic stem cell transplant (HSCT), is a treatment optionfor certain cancers. With this launch, Columbia Asia Referral Hospital Yeshwanthpur becomes one among the very few centers in India to offer allogeneic bone marrow transplants. Till now, we were doing only autologous transplants which involved the usage of the patient's own stem cells. Now, we will be able to manage conditions like high risk leukemia's, myelomas and lymphomas," said Dr Satish.

"Some of the most effective treatments for cancer such as chemotherapy and radiation are toxic to the bone marrow.The marrow produces different cells that make up the blood such as red blood cells, white blood cells and platelets. The stem cells from the bone marrow are extracted before the administration of high dose chemotherapy and then reintroduced or transplanted to the patient so that blood cell production process is re-established in the bone marrow," addedDr Neelesh Reddy, Consultant Medical Oncology, Columbia Asia Hospitals.

In fact earlier stem cells were collected only from the bone marrow in the hip bones under general anesthesia. However with advanced technology and medical supervision stem cells can now be collected from peripheral blood after giving injections. Stem cells are then harvested by simple procedure called apheresis, (in the same way as dialysis is done) and the rest of the blood is returned to the person.

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Columbia Asia Referral Hospital, Yeshwantpur Announces a Comprehensive Bone Marrow Transplant Service

Biologists grow human-eye precursor from stem cells

A stem-cell biologist has had an eye-opening success in his latest effort to mimic mammalian organ development in vitro. Yoshiki Sasai of the RIKEN Center for Developmental Biology (CBD) in Kobe, Japan, has grown the precursor of a human eye in the lab.

The structure, called an optic cup, is 550 micrometres in diameter and contains multiple layers of retinal cells including photoreceptors. The achievement has raised hopes that doctors may one day be able to repair damaged eyes in the clinic. But for researchers at the annual meeting of the International Society for Stem Cell Research in Yokohama, Japan, where Sasai presented the findings this week, the most exciting thing is that the optic cup developed its structure without guidance from Sasai and his team.

The human eye is a complex structure but the cues to build it come from inside the growing cells.

Dougal Waters/Getty

The morphology is the truly extraordinary thing, says Austin Smith, director of the Centre for Stem Cell Research at the University of Cambridge, UK.

Until recently, stem-cell biologists had been able to grow embryonic stem-cells only into two-dimensional sheets. But over the past four years, Sasai has used mouse embryonic stem cells to grow well-organized, three-dimensional cerebral-cortex1, pituitary-gland2 and optic-cup3 tissue. His latest result marks the first time that anyone has managed a similar feat using human cells.

The various parts of the human optic cup grew in mostly the same order as those in the mouse optic cup. This reconfirms a biological lesson: the cues for this complex formation come from inside the cell, rather than relying on external triggers.

In Sasais experiment, retinal precursor cells spontaneously formed a ball of epithelial tissue cells and then bulged outwards to form a bubble called an eye vesicle. That pliable structure then folded back on itself to form a pouch, creating the optic cup with an outer wall (the retinal epithelium) and an inner wall comprising layers of retinal cells including photoreceptors, bipolar cells and ganglion cells. This resolves a long debate, says Sasai, over whether the development of the optic cup is driven by internal or external cues.

There were some subtle differences in the timing of the developmental processes of the human and mouse optic cups. But the biggest difference was the size: the human optic cup had more than twice the diameter and ten times the volume of that of the mouse. Its large and thick, says Sasai. The ratios, similar to those seen in development of the structure in vivo, are significant. The fact that size is cell-intrinsic is tremendously interesting, says Martin Pera, a stem-cell biologist at the University of Southern California, Los Angeles.

The achievement could make a big difference in the clinic. Scientists have had increasing success in transplanting cells: last month, a group at University College London showed that a transplant of stem-cell derived photoreceptors could rescue vision in mice4. But the transplant involved only rod-shaped receptors, not cone-shaped ones, and would leave the recipient seeing fuzzy images. Sasais organically layered structure offers hope that integrated photoreceptor tissue could one day be transplanted. The developmental process could also be adapted to treat a particular disease, and stocks of tissue could be created for transplant and frozen.

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Biologists grow human-eye precursor from stem cells