Feb 2016

Dr. Shane Shapiro

People paying thousands of dollars for stem cell knee treatment. But does it work?

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Across the United States and in at least one Canadian city, people are paying thousands of dollars for an unproven, same-day stem cell treatment to ease pain and restore flexibility in their arthritic or damaged knees.…

Across the United States and in at least one Canadian city, people are paying thousands of dollars for an unproven, same-day stem cell treatment to ease pain and restore flexibility in their arthritic or damaged knees.

The question is: does it work?

“We don’t have any really good, level one evidence out there yet,” says Dr. Shane Shapiro, an orthopedic surgeon at the Mayo Center for Regenerative Medicine in Jacksonville, Florida. “But judging by the proliferation of practices that perform the procedure and the number of patients that have it, many people are willing to jump in without knowing whether it will or won’t work.”

Dr. Shapiro leads a 25-patient clinical trial investigating whether the bone marrow aspirate concentrate (BMAC) procedure actually relieves pain and helps knees heal in patients with osteoarthritis. Over the past three years he and a team of researchers extracted mesenchymal bone marrow stem cells from patients’ pelvises, spun them in a centrifuge to a concentrated state and then re-injected them into one knee. The other knee, serving as a control for the experiment, got a placebo injection of saline solution. Patients then underwent magnetic resonance imaging (MRI) at six months and a year to see if the knee cartilage improved from its original inflamed state.

Mesenchymal stem cells are used because they can differentiate into bone cells, cartilage cells and muscle cells. They also have anti-inflammatory qualities, which could be helpful in treating osteoarthritis. The process is considered “autologous” because the cells are reinjected into the same person who provided them, as opposed to “allogenic” transplants that involve cells donated from another person.

Dr. Shapiro expects the results to be published soon. Meanwhile, clinics offering the BMAC procedure are popping up all over and charging between $1,800 and $10,000 per injection. ”Unfortunately, now you can take a weekend course or four-day course in how to do this,” says Dr. Shapiro. “I actually don’t think that all places that you can get this done are reputable, but there are some.”

What does the FDA say?

The U.S. Food and Drug Administration (FDA) has published draft guidance documents that reflect the agency’s current thinking about such treatments. At issue is whether the procedure constitutes more than “minimal manipulation” of the cells based on the degree of processing they undergo, and represents “homologous use” — meaning the cells perform their same basic function at the site in which they are injected. The draft guidance seems to indicate the BMAC procedure meets the criteria of minimal manipulation and homologous use,

When we sought clarification, the FDA’s  Center for Biologics Evaluation and Research wrote in an email that it “expects anyone involved with human cells, tissues, and cellular and tissue-based products (HCT/Ps), including stem cells, to familiarize themselves with the regulations; they are responsible for self-assessing how the appropriate regulations apply to their products.” It added that the attributes of “processing/manipulation and intended use must be carefully evaluated on a case by case basis.”

Health Canada, which takes a harmonized approach to that of the FDA, has not yet considered whether BMAC meets minimal manipulation or homologous use criteria. According to a statement from the Biologics and Genetic Therapies Directorate, “In some cases, autologous cell therapy products that are processed for a particular patient by a regulated health professional pursuant to the scope of their practice may not require federal pre-market regulatory authorization under the Food and Drug Regulations.”

In 2014 the U.S. Federal Appeals Court ruled in FDA’s favour in a case against Regenerative Sciences, a Colorado-based organization that until 2010 had been offering the BMAC treatment with cells that were extracted, cultured to make them more robust, and then re-injected into the patient. The organization now offers the treatment — called Regenexx-C (for “cultured,” a process that takes several days) — only at a clinic in the Cayman Islands, beyond the FDA’s jurisdiction. They continue to offer Regenexx-SD (for “same day”) at the Centeno Shultz Clinic in Colorado and at a network of clinics around the United States.

At a recent webinar, Dr. Christopher Centeno said that while “there are some additional regulations that may be coming out on stem cell therapies,” he didn’t anticipate that “any of those are going to change what happens here at Regenexx” and added that “right now there are no FDA guidelines for this type of work.”

The BMAC procedure should not be confused with stromal vascular fractioning (SVF) in which adipose (fat) cells are drawn from a patient by liposuction, run through a centrifuge to isolate the stem cells and then re-injected into the patient’s damaged knees or hips or shoulders. In fact, many clinics offer the treatment for a laundry list of conditions and diseases. Because SVF breaks down and eliminates the structural components of the adipose cells, it goes beyond the limits of minimal manipulation, according to the FDA. The agency has begun cracking down on clinics offering the procedure.

Here in Canada, clinics are offering BMAC procedures, says Dr. Jas Chahal, an orthopedic sports medicine surgeon with the Women’s College Hospital and the University Health Network in Toronto. “You can get it done. I’m not sure if you can get it across Canada, but there are people doing it in the Greater Toronto Area, for sure.”

Canadian study goes beyond BMAC

Dr. Chahal says more study is needed to prove whether the BMAC procedure is effective. “If you look at some of the articles presented at conferences, the basic science evidence shows that there could be a benefit — there are some anti-inflammatory molecules in there and there are some growth factors. I just don’t think it’s been adequately studied.”

Dr. Chahal and his team are midway through conducting a clinical trial that goes well beyond the same-day BMAC procedure. They are extracting the mesenchymal bone marrow stem cells from their patients and doing ex-vivo expansion (ramping up the number of cells in a lab) and then re-injecting them at concentrations of 1 million, 10 million and 50 million cells. “We’ve enrolled 12 patients and treated six so far,” says Dr. Chahal. “We expect to treat the next six in the next six months and should have data in another year.”

Should the Mayo Clinic study show positive results, Dr. Shapiro expects it could take some time for the BMAC procedure to become standard treatment for osteoarthritis. For one thing, there’s the cost.

“Someone has to pay for this,” says Dr. Shapiro. “If you’re going to be delivering it to millions of people, it has to come down in cost. It’s got to be more efficient and there’s got to be a system where it’s covered under either public or private health insurance, so that we could deliver it to the large number of people who need it.”


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Dec 2015

Dr. Eva Feldman

Major trial for ALS therapy in the works

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Dr. Eva Feldman devoted 12 years to working on a drug-based cure for amyotrophic lateral sclerosis (ALS).  It was, she says, “a very big endeavour.”  It failed.…

Dr. Eva Feldman devoted 12 years to working on a drug-based cure for amyotrophic lateral sclerosis (ALS).  It was, she says, “a very big endeavour.”  It failed.

So, in 2006 the University of Michigan clinician/researcher took a sabbatical to rethink her approach to fighting ALS, the cruel, fatal condition that attacks the nerve cells (neurons) that control muscle movement.  “I wanted a break,” she says.  In California, Dr. Feldman found scientists doing interesting animal studies on treating spinal cord injury with stem cells. It changed her perspective entirely.

Today, with two early-stage human studies behind her, Dr. Feldman hopes to soon begin a large-scale clinical trial to test whether human neural stem cells injected into the spinal columns of ALS patients can stop the disease from stealing their ability to walk, talk, eat and breathe.

“We inject the cells into the high part of the spinal cord of patients with ALS with the goal of protecting the large motor neurons that are necessary to maintain normal breathing.  Our goal is for the stem cells to go into that area, surround the neurons that are starting to get ill and nurse them back to health.  We do very similar injections in the lumbar area of the spine to preserve the neurons that go to the muscles that allow patients to walk.”

Preclinical studies she and her team conducted on rats and pigs showed that the stem cells “take a really bad environment and clean it up.” Inflammation is ameliorated and the stem cells surround the large, ailing motor neurons and nurse them back to health. “The cells go from looking like they are about to die to being quite healthy and robust,” says Dr. Feldman.

Phase I and II clinical trials involving 30 patients went “extremely well,” she says, with the procedure proven to be safe and the patients able to tolerate the accompanying immuno-suppressant therapy. “We have good preliminary data,” she says.

Neuralstem Inc., Dr. Feldman’s industry partner in the project, is organizing a large, multi-centre trial in 2016 to test whether the procedure truly works. Richard Garr, the company’s Chief Executive Office, is understandably guarded about the details, saying via email that his company is working with the U.S. Food and Drug Administration and that “all of the issues with respect to the scope and nature of the trial are still being determined.”

Dr. Feldman, who has been down this road before with the failed ALS drug, is cautiously optimistic.  “As enthusiastic as I am about the therapy, until we do a very large trial we simply won’t know with certainty that this is the hopeful home run that we want it to be.”

For Ted Harada, a 43-year-old former FedEx manager in Atlanta, Dr. Feldman’s stem cell therapy has been a life-saver. The recipient of two stem cell implant surgeries, he has seen his decline from ALS virtually stopped.  The normal survival period for ALS, which is sometimes called Lou Gehrig’s disease after the New York Yankee slugger who succumbed to it, is about 36 months. He is now five years out and feeling good, although he still has the disease.

“I put my cane down two or three weeks after the (second) surgery and I haven’t picked it back up,” he says.  “When I had my fifth year anniversary, my doctor said ‘Ted, I would have guaranteed you’d be dead within two or three years when I first met you.’  I like to say that the surgeries set the clock back to what I call onset.”

Dr. Feldman says other patients in the studies also have done well but “the numbers are small … until our numbers are larger we can’t say with certainty.”

While criteria haven’t been set, participants in the larger trial likely will need to be in the early stages of the disease, with the ability to breathe reasonably well and speak and swallow without difficulty. Dr. Feldman says Canadian patients might be eligible if they can travel to a surgical site — but, again, details are still being worked out.

Dr. Feldman is also excited about the possibility of using the same kinds of stem cells to treat the dementia disease.

“I have beautiful preclinical data in animal models of Alzheimer’s. We’ve shown that the injection of stem cells into the selected areas of the brain that are required to form new memories rescues the animals and they are able to function normally. We see the accumulation of amyloid, which is the build-up of plaque that patients get, gone. The stem cells go in and they are just like garbage disposals, cleaning up all the garbage.  It’s remarkable.”



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Aug 2015
Jeff Biernaskie Screen Captuer

Jeff Biernaskie

Researchers ask burn survivors: ‘What would make life better?’

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When Dr. Jeff Biernaskie and his University of Calgary Skin Regeneration Team set to work to build better skin grafts with stem cells, they wanted to talk to those with the most at stake: burn injury survivors.…

When Dr. Jeff Biernaskie and his University of Calgary Skin Regeneration Team set to work to build better skin grafts with stem cells, they wanted to talk to those with the most at stake: burn injury survivors.

“I came into this without the experience of working with patients,” says Dr. Biernaskie, an assistant professor in stem cell biology. “So I got together with a burn physician Dr. Vincent Gabriel, to ask, ‘What are the deficiencies somebody faces when they’ve had a burn and a skin graft?’ We wanted to ask them, ’What would make your quality of life better?’”

The team is conducting patient surveys to find out how burn survivors feel about their grafts, what their expectations are and how their priorities change over time.  They are also asking how burn survivors feel about stem cell transplants to regenerate dermal tissue — the thick layer under the epidermis that contains blood capillaries, nerve endings, sweat glands and hair follicles.

“It’s a different kind of pain in the beginning than it is later — often chronic itch is more problematic than pain in the long term” says Dr. Biernaskie. “A year later, you also may have limitations on mobility because of scarring.  So you may have a very different perspective on what you’d be willing to accept in terms of the risks — for example, the risk of aberrant growth, which might require additional surgeries — or the potential of failure of the stem cell transplant.

“These are real concerns, but by talking to patients living with skin grafts, our goal is to identify their most critical deficiencies and then design therapies to address those, so that any potential shortcomings are outweighed by the potential gains in function.”

The survey findings will help guide the Skin Regeneration Team as they move closer to conducting clinical trials on human patients. Right now, they are transplanting human dermal stem cells into skin-grafted mice, and seeing positive results.

“We’re seeing the cells respond in the appropriate ways, spreading out across the area of the graft.  What’s impressive to me is to see that the cells actually move up into the skin graft and interact with the epidermal cells, repopulating parts of the graft that may have been deficient. By regenerating new dermis, we hope that we can positively affect the function of the overlying epidermis, which otherwise is typically quite fragile after split thickness skin grafting. The cells are starting to secrete a lot of the collagens and the other factors needed to remodel that skin.”

They hope to be testing the stem cell transplants in larger animals such as pigs, which have skin more similar to that of humans, within two years.

“We want to look at the innervation (interaction with the nerves) of the graft, vascularity of the graft, as well as the histological (anatomical) functions of the graft.  All these things need to be looked at to see how much of an impact we’re having.”

Ultimately, the goal is to use the burn patient’s own skin cells to create millions of dermal stem cells that can be used for transplant, an autologous procedure that limits the risk of rejection and the need for immunosuppression drugs.

The team has cell biologists working on characterization of adult dermal stem cells — drawing them out of skin from an adult human and understanding the biology behind them.  They are also working with bioengineers to explore how to expand the cells using bioreactors to rapidly generate the large numbers of cells needed.

“We want to develop an autologous cell-based therapy to regenerate the dermis — that’s really our goal,” says Dr. Biernaskie. “I’m optimistic.  We can readily get the cells out from a patient, we’re able to grow them up from relatively small numbers of starting cells and we’re working on different matrices and scaffolds to improve survival and integration once they’re grafted in.”

He is even more optimistic about using stem cells to treat chronic skin wounds.

“Think of elderly patients with chronic wounds who are having their dressing changed every three days or so. That’s a lot of nursing costs, and bandages.  And it’s grueling for the patients. If you could take a biopsy, grow up a few hundred millions of cells, and then repopulate a chronic wound in order to get it to close and re-epithelialize, that would really have an impact on quality of life — and on the associated health care costs. That’s something we’re going to look at.”

The work being done by the Skin Regeneration Team is supported by Alberta Innovates Health Solutions and the Calgary Firefighters Burn Treatment Society.

Current care for burn injuries:
The current standard care for deep burns is split thickness skin grafting, which involves taking epidermis (outer) and part of the dermis (inner) layers of skin from elsewhere on the patient’s body and then grafting it onto the burn site.  Short term, the process is painful. Long term, additional grafts are often needed and the transplanted skin tends to scar, which can severely limit mobility, and are extremely fragile, leading to frequent wounds.  Also, the grafted skin is devoid of dermal appendages, such as sweat glands and hair follicles.

The potential stem cell solution:
Researchers hope stem cells drawn from the patient’s healthy skin can be coaxed to create millions of precursor cells than can be seeded into the dermal layer of the burn wound to generate new skin tissue that will fully integrate with the epidermal layer and help to grow new dermal appendages. The hope is that this regenerated tissue will be less prone to scarring and bleeding and provide better overall function.

[Find out more about stem cells and wound healing here.]

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Aug 2015
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Dr. Ivar Mendez

A stem cell solution to Parkinson’s?

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Parkinson’s, is not a kind disease. As dopamine-generating cells in their brains deteriorate, patients must deal with tremors; their feet may suddenly seem to freeze to the floor; they may have difficulty swallowing.  …

Parkinson’s, is not a kind disease. As dopamine-generating cells in their brains deteriorate, patients must deal with tremors; their feet may suddenly seem to freeze to the floor; they may have difficulty swallowing.  Walking becomes a stiff-limbed shuffle.

While drugs such as levodopa and dopamine agonists have greatly enhanced quality of life for Parkinson’s patients, their effectiveness diminishes over time. Deep brain stimulation has also proved helpful, but it does not slow the pace of neurodegeneration.

Stem cell transplants, however, may offer a longer-lasting solution.

“I think Parkinson’s is going to be the first neurological condition where stem cell therapy will be used widely,” says Dr. Ivar Mendez, Unified Head of the Department of Surgery at the University of Saskatchewan.  “We’re looking at transplanting one cell type. So we can direct the stem cells to become that type of cell — a Group A9 dopaminergic neuron.”

Transplanting cells into the brains of Parkinson’s patients in the hope of restoring dopamine neurotransmission is nothing new: it’s been going on for more than 25 years.  The results, according to a 2013 report in The Lancet, “have been variable and, thus, the merits of this approach have been both questioned and championed.”

The variation in results has been attributed to, among other things, the use of different strategies or protocols for transplanting the cells.  A key Canadian contribution to solving that problem is the Halifax Protocol for injecting cells into the human brain. Developed by Dr. Mendez, who was then at Dalhousie University, in collaboration with researchers from Toronto, Montreal and Calgary, the Halifax Protocol is regarded as the gold standard for effective brain repair using cell implantation.

“We developed the methodology for clinical transplantation,” says Dr. Mendez.  “When reviewers looked at all the grafts of all the patients who have been transplanted across the world, it was felt that ours did the best, in large part because of the methodology we developed.”

Dr. Mendez is working with fellow Parkinson’s stem cell pioneer Dr. Ole Isacson of Harvard to use induced pluripotent stem cells created from skin tissue to make dopamine-generating cells that, once transplanted, will integrate into the brain circuitry and restore motor function.

The process is autologous, meaning the stem cells come from the patient themselves, so no immunosuppression therapy is required. As well, researchers have come up with ways to generate the millions of cells required and have developed processes to make those cells robust enough to do the job.  So far, tests with large animals have shown positive results.

“We are continuing to work with animal models until we’re ready to start on a clinical trial, which should go ahead probably in the next two to three years,” says Dr. Mendez. “But I’m always concerned not to build unnecessary expectations among people affected by the disease.”

Other research centres are also working on a stem cell solution to Parkinson’s, with clinical trials using fetal cells currently underway in the United Kingdom.

“We’re very enthusiastic,” says Dr. Mendez. “Resolving the issue on a long-term basis, that is really the attraction. If one cell deteriorates or degenerates with time, can we actually replace that cell and reconstruct the circuitry? If we can, it’s a one-shot procedure. You do it only once and then the transplant will integrate into the host.”

Such a solution, however, could still be many years away.  Researchers need to be sure the cells they inject will do the intended job, without causing additional problems or perhaps generating tumours.

“We’re quite advanced in terms of realistically looking at a clinical trial,” says Dr. Mendez. “But we have to make sure that the preclinical scientific evidence is solid to ensure success”

[Find out more about stem cells and Parkinson’s here.] 

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May 2015

Dr. Mark Freedman

Beyond damage control: can MS be fixed?

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When it comes to treating multiple sclerosis (MS), Dr. Mark Freedman would like to move beyond damage control.

“We can limit, to some extent and in some cases completely, the damage,” says Dr.…

When it comes to treating multiple sclerosis (MS), Dr. Mark Freedman would like to move beyond damage control.

“We can limit, to some extent and in some cases completely, the damage,” says Dr. Freedman, a clinician/researcher at the Ottawa Hospital Research Institute. “But fixing the damage that’s been done? Not yet. “

Fixing the damage done by MS is the ultimate goal of a new $4.2-million clinical trial that Dr. Freedman is co-leading with Dr. James J. Marriott of the University of Manitoba in Winnipeg.  It’s called MESCAMS (for MEsenchymal Stem cell therapy for CAnadian MS patients).

“The excitement surrounding the MESCAMS has been tremendous,” says Yves Savoie, President and CEO, MS Society of Canada, a major supporter of the clinical trial.  “Not only is Canada fortunate to have two  trial sites in both Ottawa and Winnipeg – accepting a total of 40 Canadian participants – but MESCAMS is also part of a larger international research effort studying mesenchymal stem cells that pools scientific resources and expertise from nine countries. This level of collaboration will yield important answers about the efficacy of cell-based treatments.”

Found mostly in the bone marrow, fatty tissue and cartilage, mesenchymal stem cells have a natural anti-inflammatory effect that makes them an intriguing possibility for treating MS, which occurs when a person’s immune system attacks and inflames the protective sheath (myelin) covering nerves. Myelin damage snags the signals that flow from the brain through the nervous system to the rest of the body.

“These cells possibly will act like anti-inflammatory drugs to control the disease,” says Dr. Freedman. ”But what we’re really looking for is the potential for something to heal up, for a sign that these cells are doing something.  Other people have noted it in the optic nerve system, which is actually an extension of the brain and is affected by MS.”

Readers may be familiar with the story of Jennifer Molson, the Ottawa woman whose MS symptoms were eradicated by a stem cell bone marrow transplant conducted by Dr. Freedman and Dr. Harry Atkins as part of an earlier clinical trial. Each trial participant underwent a harrowing course of chemotherapy that virtually destroyed their immune system before being given a fortified version of their own bone marrow stem cells to rebuild it. With MESCAMS no such chemo bombardment is necessary.

“We don’t exactly know why Jennifer, and others in the trial, recovered. We think the reason is we were able to curb the inflammatory response to the point where the body could heal.  These cells that we’re using (mesenchymal stem cells) have been shown, at least in early studies in humans, to repair — period. But they happen, at the same time, to have an anti-inflammatory effect. So they may be able to accomplish both things together. And without the need of any chemo, there is very little risk to the people taking it.”

The real challenge, says Dr. Freedman, will be measuring — and scientifically documenting — repair, if it happens. “When was the last time you heard something that could repair things in MS? Nobody’s been able to show it.  So we’re hoping we will be able to see it and measure it. That’s the real goal of this study.  If we can all show the same signal through nine or 10 sites around the world doing this, then we’re going to have the evidence we need to move to the next stage, which is doing this en masse with people who have already acquired damage . That’s what our MS patients are all hoping for.“

However, Dr. Freedman urges caution.  This is an early stage clinical trial. If the mesenchymal stem cells do affect repair, it may be minimal. “The primary outcome is going to be the effect on gadolinium-enhanced lesions in MS as shown by MRI. It will prove whether we have biologically viable cells capable of creating an effect that can be measured in humans.  It may sound trivial, but it’s never been done.”

Editor’s Note: MESCAMS organizers have published a Frequently Asked Questions page about the trial here (  Full eligibility criteria are available here(



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Oct 2014
1 Comment

Dr. Timothy Kieffer

A step closer to curing diabetes

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The news that Dr. Timothy Kieffer’s team at the University of British Columbia, in collaboration with New Jersey based BetaLogics, has found a faster way to create insulin-producing cells is the latest example of how Canada has been a world leader in fighting type 1 diabetes.…

The news that Dr. Timothy Kieffer’s team at the University of British Columbia, in collaboration with New Jersey based BetaLogics, has found a faster way to create insulin-producing cells is the latest example of how Canada has been a world leader in fighting type 1 diabetes.

It was Canadian Sir Frederick Banting, working with medical student Charles Best, who discovered insulin in 1922 — a breakthrough that has rescued the lives of millions of diabetics around the world.  In the late 1990s, a team of researchers and doctors at the University of Alberta developed the Edmonton Protocol, a procedure for implanting pancreatic islets to treat patients with type 1 diabetes mellitus. However, widespread adoption of the protocol has been limited by the shortage of donor tissue — it can take as many as three donated pancreases for each patient.  Also, recipients need to take strong immunosuppressive drugs to prevent rejection of the transplanted cells.

What Dr. Kieffer and his collaborators have come up with — a protocol to turn stem cells into reliable, insulin-producing cells in about six weeks, far quicker than the four months it took using previous methods — represents a significant advance.  It brings scientists a step closer to being able to produce an unlimited supply of insulin-producing cells to treat this devastating disease that affects more than 2 million Canadians and almost 400 million people worldwide.

According to a UBC media release, the protocol transforms stem cells into insulin-secreting pancreatic cells, called S7 cells, via a cell-culture method. The conversion is completed after the cells are transplanted into a host. Tested on mice, the transplanted cells were successful in rapidly reversing diabetes.

We asked Dr. Kieffer to answer a few questions about the discovery, the results of which have been published in Nature Biotechnology, which you can read here. Here’s what he had to say:

Question: What’s the key advance here – that you can now make insulin producing cells much more quickly or that you can reverse diabetes so effectively?

Answer: The key advance with our work is the development of culture conditions to extend the maturation of the cells well beyond the pancreatic progenitor stage that we and others have previously achieved.  The cells have many characteristics of mature insulin producing beta-cells at the time we transplant them, and thus are able reverse diabetes in about one-quarter the time needed with pancreatic progenitor cells, and with only one-quarter of the cell dose.

Question:  You developed the protocol for these S7 cells with mice. How far away are you from human trials?

Answer: The protocol for cultivating the cells was developed with humans in mind, not mice.  Therefore, human cells and scalable methods for cell manufacturing were used.  Testing the cells in mice with diabetes represents an important and necessary step on the path to clinical trials.  It will be up to regulatory agencies such as Health Canada to determine what other studies are required before clinical testing can begin.  In this regard it is very encouraging that the FDA recently approved the clinical testing in patients with type 1 diabetes of pancreatic precursor cells produced by ViaCyte.

Question:  Do you see a day in the next 10 years when this kind of treatment replaces daily insulin injections?

Answer: I am quite enthusiastic for the potential of a stem cell based therapy for diabetes.  The clinical path has been proven with islet transplantation — only a few teaspoons of insulin producing cells (cadaveric islets) are infused into the patients and with this, effective glucose control can be re-established.  It is only a matter of time before stem cells provide the needed source of cells to replace insulin injections, and I predict this will be within 10 years.

Question:  You’re working with BetaLogics Venture of Janssen Research & Development, LLC on the protocol. Do you have plans to commercialize the protocol as a treatment?

Answer: The work by Dr. Alireza Rezania and colleagues at BetaLogics Venture was instrumental in this research; these are the scientists who significantly advanced the differentiation protocol.   The involvement of Janssen greatly increases the chances that this stem cell strategy will develop into a product, with the hopes it will not only treat diabetes, but ultimately cure it.

(Note: This research is supported in part by funding from JDRF, the Canadian Institutes of Health Research Regenerative Medicine and Nanomedicine Initiative, and the Stem Cell Network.)

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Sep 2014

UK researchers post ‘encouraging’ results in stroke study

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The sample size is far too small to prove much yet, but doctors in Britain have seen “very encouraging” results from a new therapy that delivers stem cells extracted from patients’ bone marrow to their brains within days of having suffered a stroke.…

The sample size is far too small to prove much yet, but doctors in Britain have seen “very encouraging” results from a new therapy that delivers stem cells extracted from patients’ bone marrow to their brains within days of having suffered a stroke.

According to a report published in August in Stem Cells Translational Medicine,  all five patients who took part in the pilot study showed improvements over a six-month follow-up period.

This is significant because all but one of the five had the most severe type of stroke from which only four per cent of patients usually recover and regain independence. A story carried in the Daily Mail reported that  all four of these severe-stroke patients were alive and three were independent after half a year.

In the trial, believed to be the of its kind, the patients received purified CD34+ cells,  which are stem cells found in the bone marrow.  The patients got the these cells within a week of their attacks (in previous studies stem cells were infused months afterwards) to release  chemicals to spur  growth of new tissue and blood vessels in the parts of the brain damaged by stroke.

Dr Soma Banerjee, a lead author and Consultant in Stroke Medicine at London’s Imperial College Healthcare NHS Trust, urged caution:  “This study showed that the treatment appears to be safe and that it’s feasible to treat patients early when they might be more likely to benefit. The improvements we saw in these patients are very encouraging, but it’s too early to draw definitive conclusions … We need to do more tests to work out the best dose and timescale for treatment before starting larger trials.”

Should the therapy prove effective in larger scale clinical trials, the implications are enormous. Stroke is a major killer and disabler.  According to the Heart and Stroke Foundation, there are 50,000 strokes in Canada each year — a rate of one every 10 minutes.

The University of Toronto’s Dr. Cindi Morshead, whose research explores using stem cell s in regenerative medicine, called the study “quite comprehensive.”  She pointed out that the researchers screened more than 80 potential candidates for the study before selecting the five who got the treatment. “It was a safety trial so they really had to be careful in their selection.  But five out of 80 people able to benefit from this, that’s still pretty good. ”

As someone who works in the field, she’s optimist about the results. “My takeaway is that it’s exciting. Two of the people in the study were quite young: 45 and 47. It’s hugely significant — they’ve only lived half their lives.”

For a comprehensive look at using stem cells to treat stroke, click here.





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May 2014
Marc Turner Screen Capture

There will be (stem cell derived) blood

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Over the next three years, a team of Scottish scientists hope to prove that the blood they are making from stem cells is as good as — or even better — for transfusions than the ordinary donated kind.…

Over the next three years, a team of Scottish scientists hope to prove that the blood they are making from stem cells is as good as — or even better — for transfusions than the ordinary donated kind.

Although it has hardly raised an eyebrow in Canada, this potentially game-changing research has been big news in the United Kingdom where it was featured in the Daily Mail, a splashy tabloid with a circulation of 1.75 million. As the Mail suggested, this “could lead to a future where artificial blood is used more regularly than donated blood.”

Prof. Marc Turner, pictured left, leads a lab at the University of Edinburgh that has successfully produced red blood cells from human embryonic stem cells and induced pluripotent stem cells (stem cells drawn from the skin that are reprogrammed to an embryonic-like state).  The researchers have made a careful study of the cells’ properties in test tubes and Petri dishes. “But the only real way of finding out if these are the Real McCoys and that they fit in the circulation the same way as normal red blood cells is do a proof of principle, ‘first in man’ study,”  says Prof. Turner, the Medical Director at Scottish National Blood Transfusion Service  and leader of the  £5 million ($9.27 million) project.

How could this stem cell derived blood be better? The human body produces millions red blood cells every minute of every hour. These cells, which transport oxygen around the body via their hemoglobin content, last about 120 days.  So when you donate blood at your local clinic, some of it might be 119 days old and ready for the scrap heap. Stem cell generated red blood cells, however, are all brand, spanking new.  Ideally, then, they should all put in a good four months’ work in the bloodstream after transfusion. That’s what Prof. Turner’s team wants to find out.

The Scots aren’t the first to do this. In a 2011 paper published in BloodFrance’s Dr. Luc Douay showed that red blood cells derived from adult stem cells performed “favorably” compared to “native red blood cells” when transfused into a test subject.  As well, labs around the world have been successful in producing red blood cells using embryonic stem cells and induced pluripotent stem cells.

The problem has been “scaling up” the number of red blood cells required to do clinical trials. Dr. Douay used hematopoietic (blood-based) stem cells for his breakthrough.  “But researchers don’t have culture conditions that can support a very large expansion of hematopoietic stem cells,” says Dr. Julie Audet, Associate Professor of Biomedical Engineering at the University of Toronto.  “So this step of amplification of the starting material is causing problems.”

Another challenge, says Dr. Audet, is that red blood cells derived from embryonic or induced pluripotent stem cells lack maturity: the hemoglobin they carry is more like the stuff of newborns than that of adults.

While Prof. Turner acknowledges the fetal quality hemoglobin isn’t ideal, it is functional. “It will do for the time being. We have some ideas about how we might try and nudge the cells to an added degree of maturity.  It’s important, but it’s not a showstopper at this stage.”

As for the “scaling up” challenge, he thinks they have that figured out — at least for their current very small (three-patient) study. “It will only require relatively modest volumes of red cells. After that, on the big assumption that that we will be successful, we will be looking to go into proper clinical study. That’s when we will start to confront the issues of scale up.”

So what does it all mean? Are blood donor clinics destined to go become a relic of a bygone era?

Not any time soon, says Prof. Turner.

“This is years or decades away. We don’t want people to stop donating blood just now, please.”

The more immediate application, he says, could be using the process for people with thalassemia, a genetic disorder that causes destruction of red blood cells.

“These patients are dependent on long-term red blood cell transfusions. They survive well now compared to decades ago, but they do have a problem with iron loading. One of the potential advantages of having a younger cohort of red cells is they should last longer in circulation. That would offer a clinical advantage.”

So the potential short-term impact is important, but limited. Longer term, however, this could change everything.

“In the very long term, it may be possible to generate red cells for general use,” says Prof. Turner.

“That obviously would have an advantage in those countries that don’t have a secure supply of blood. Developed countries like Canada and the UK have sufficient sources of cells and pretty secure and safe blood supplies. But we shouldn’t take that for granted.  Certainly, we’re all familiar with problems with (transfusion transmitted) infections in the past, like Hepatitis C. And we’ve had problems with Creutzfeldt–Jakob disease here in the UK.”

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Apr 2014
JulieLessard IRIC 2-cropped

Gene that regulates leukemia will take time (and patience) to tame

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While patience is a virtue for most of us, it is an absolute prerequisite for stem cell researchers.

The recent news that scientists have identified a gene called BRG1 that appears to regulate leukemia stem cells marks an important advance in understanding the dread disease.…

While patience is a virtue for most of us, it is an absolute prerequisite for stem cell researchers.

The recent news that scientists have identified a gene called BRG1 that appears to regulate leukemia stem cells marks an important advance in understanding the dread disease. It also signifies years of work by the team led by Dr. Julie Lessard at the Institute for Research in Immunology and Cancer (IRIC) of Université de Montréal.

“About four years,” says Dr. Lessard, pictured left, one of Canada’s leading researchers in the field of hematopoiesis — the art of blood production.

Using mice as subjects, Dr. Lessard’s team found that removing the BRG1 gene left the leukemia stem cells and progenitors unable to survive, divide and make new tumors, permanently shutting down the cancer.  But while they are delighted with their findings, the researchers know they are in for many more years of work.

“We need to identify BRG1 inhibitors that will work in vitro (in test tubes and Petri dishes) and in vivo (with animals and humans),” says Dr. Lessard. “We believe that it is the ATPase activity that is the essential function we need to target for potential drug development, so that’s what we’re going after.”

In essence, that means finding small molecules that can stifle BRG1, the research equivalent to finding a needle in a haystack. Fortunately, IRIC is equipped with computer-driven high throughput screening to search their library of about 120,000 molecules for one that will do the trick. “We are hoping we can get there in the coming years,” she says.

Dr. Lessard’s findings further strengthen Canadian leadership in the field of stem cells and hematopoiesis. It was two Ontario Cancer Institute researchers — Drs. James Till and Ernest McCulloch — who first proved the existence of stem cells in the early 1960s while trying to find new treatments for leukemia. Dr. John Dick, of Toronto’s University Health Network, first identified tumour-initiating cancer stem cells in 1997.

What’s particularly intriguing about Dr. Lessard’s findings is that shutting down the BRG1 gene only appears to affect leukemia-generating stem cells. “Its function in the normal stem cell is rather modest. So you can take the gene out of leukemic cells and it will shut them down without shutting down the other stem cells you need to continue growth.”

While Dr. Lessard is excited about this project, she’s realistic about the amount of time and work involved.

“First of all, we have to have a very solid preclinical product to test in animals.  We think that a therapeutic window must exist. And this is what makes this study more interesting. It will be very exciting to explore in the coming years.”

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Apr 2014
Mini-heart Screen Capture

Thinking outside the heart

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Stem cell derived mini-heart can pump blood through sluggish veins

A U.S.-based researcher has come up with what she believes is a stem cell solution for sluggish blood flow that could knock the socks off the current standard of care.…

Stem cell derived mini-heart can pump blood through sluggish veins

A U.S.-based researcher has come up with what she believes is a stem cell solution for sluggish blood flow that could knock the socks off the current standard of care.

“Compression stockings have been used since antiquity,” says Dr. Narine Sarvazyan, a researcher at George Washington University in Washington, DC. “So we really haven’t made much progress in treating chronic venous insufficiency.”

The condition is common, affecting between 20-30% of people over the age of 50. It can be particularly distressing for people with diabetes, causing non-healing ulcers to form on their legs or ankles. It can also affect people who are paralyzed and those recovering from surgery.

Dr. Sarvazyan’s solution is to implant a “mini-heart” made of stem cell derived heart muscle cells called cardiomyocytes at the site where the blood is stagnating.  The cells form a cuff that wraps around the problem vein while rhythmically contracting and releasing to move the blood along. You can see a short video of how it works here.

The invention of the mini-heart has caused quite a stir online.  It has been picked up by the Huffington Post, Science Daily and Business Standard

So far, Dr. Sarvazyan has only created “in vitro” (Petri dish) versions of the mini-hearts in her lab. Her next step, after finalizing the design, will be to move to animal tests with rats and, ultimately, pigs. In a best-case scenario, she hopes to begin clinical trials with people after about two years.

The advantage is the mini-hearts can be tailor-made from stem cells extracted from the patient’s own fatty tissue so that there will be no danger of rejection and little risk of inflammation.

“It’s a very different application,” says Dr. Sarvazyan. “Most people who work with these cardiomyocytes have a goal of repairing cardiac muscles. That is pretty much where everyone is aiming.  But the idea came into my mind that we can use the same tissue and actually use it in different locations much more easily. You don’t have to have that much structured muscle. It doesn’t have to have much force. It’s easier to vascularize because it’s smaller.”

Dr. Sarvazyan outlines the advantages in a paper called Thinking Outside the Heart, published, in the Journal of Cardiovascular Pharmacology and Therapeutics.

“So far I don’t see any downsides,” she told Stem Cell NewsDesk.  “Of course, nature is much smarter than us. It’s possible when we put it in animals, something may happen that we could not predict.  I can’t say for sure that it will work — we definitely need to test it.”

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