Joe Sornberger

02
Oct 2013
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Klaassen CBC Screen Capture

Cord blood: Now Canada can bank on it

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Bad news, they say, travels fast. But the announcement this week that Canada now has a national public cord blood bank up and running (or, more appropriately, taking its first baby steps) shows that good news is no slowpoke.…

Bad news, they say, travels fast. But the announcement this week that Canada now has a national public cord blood bank up and running (or, more appropriately, taking its first baby steps) shows that good news is no slowpoke.

Mothers delivering at two Ottawa Hospital campuses now have the option of depositing their babies’ umbilical cord blood into the National Public Cord Blood Bank. It can then be withdrawn to save the lives of some of the 1,000 Canadians who, at any given time, need an unrelated stem cell match to treat diseases such as leukemia, lymphoma, thalassemia, sickle cell anemia and TaySachs.

Dr. Robert Klaassen, left, a hematologist/oncologist at the Children’s Hospital of Eastern Ontario in Ottawa, explained to CBC News that having a national cord blood bank will shorten wait times and increase the pool of potential matches: “The main problem we have is that many patients, when they need a bone marrow transplant, don’t have a sibling to match to so we have to start looking for unrelated matches.”

Canada, the country where stem cells were discovered, has been slow off the mark with this. Postmedia newspapers pointed out that until this week ours was the only G8 country without a national cord blood bank.

While there currently are three other regional cord blood banks, (Héma-Québec, Alberta and Victoria Angel) and several private operations, Canadian patients needing stem cell transplants often have had to be treated with supplies purchased from other countries – at a cost to the health care system of about $42,000 per unit.

According to Canadian Blood Services (CBS), which manages the national bank, a Made In Canada cord blood unit will be substantially less than half that amount.

CBS will roll out three more collections sites in Brampton, Edmonton and Vancouver by mid-2014 and expects to collect 18,000 donated cord blood units over the next six years. Those cities were selected because of their high birth rates and diverse ethnic populations, which will boost the range of possible matches.

As Sue Smith, CBS Executive Director of Stem Cells, told CTV News, “It’s very easy; any woman over the age of 18, as long as they have had a healthy birth and it’s beyond 34 weeks gestation, [can donate].”

The National Cord Blood Bank is a $48-million enterprise with provincial and territorial ministries of health (except Québec) investing the lion’s share while CBS leads a $12.5-million fundraising campaign for the rest. As of this week they have raised more than half that amount.

So, more lives will be saved and significant cost savings realized. If that’s not good news, what is?

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27
Sep 2013
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Stem Cell Animation 2

Take a minute to understand stem cells

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If you have struggled to understand what stem cells are all about, take comfort: you are not alone. I wrote the book on them and I can still stumble over concepts like self-renewal and differentiation and plasticity.…

If you have struggled to understand what stem cells are all about, take comfort: you are not alone. I wrote the book on them and I can still stumble over concepts like self-renewal and differentiation and plasticity.

Fortunately there is now an excellent resource to help those of us with less than keen scientific minds to quickly get the picture – quite literally.

Ben Paylor, a PhD candidate at the University of British Columbia, and Dr. Mike Long, a post-doctoral fellow have produced StemCellShorts, three short animated videos that manage to explain tricky science concepts clearly without dumbing things down.

The series is being released this fall, with the “world screening premiere” during the Till & McCulloch Meetings (the annual gathering of Canada’s best and brightest stem cell scientists) in Banff Oct. 23-25. But you can  view the first in the series here. It answers the question, What is a stem cell?

Dr. James Till narrates the minute-long, action-packed piece and is the perfect person to do it.  In the early 1960s, he and his research partner Dr. Ernest McCulloch set out the core principles of stem cell science.

The other two videos in Phase 1 of the project include  ‘What is an embryonic stem cell?’ narrated by Dr. Janet Rossant, Chief of Research at SickKids Hospital, and ‘What is an induced pluripotent stem cell?’ voiced by Dr. Mick Bhatia, Director of the McMaster Stem Cell and Cancer Research Institute.

Production was funded through a Public Outreach Award provided by our sister organization, the Stem Cell Network. The Foundation is partnering with the Network on Phase 2, which will see five more animated shorts that should be ready by the spring.

In the meantime, enjoy the first instalment. A minute later, you’ll feel scientifically smarter.

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26
Sep 2013
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L. Jacques Menard

Outstanding Quebec business leader joins Foundation Board

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If an organization, like an individual, is known by the company it keeps, then the Canadian Stem Cell Foundation is further solidifying its reputation for sterling leadership.…

If an organization, like an individual, is known by the company it keeps, then the Canadian Stem Cell Foundation is further solidifying its reputation for sterling leadership.

The Foundation’s Board of Directors, which already includes some of Canada’s leading figures in business, medical science and public policy, has been further bolstered by the addition of L. Jacques Ménard, the Chairman of BMO Nesbitt Burns and President of BMO Financial Group, Quebec, to its ranks.

Not just one of Canada’s great financial leaders, Mr. Ménard, has made important impacts on his community, province and country.  He was recognized as a Great Montrealer in 2009 by the city’s Board of Trade, named Officer of the Order of Québec in 2010, and, in 2012, was promoted to Companion of the Order of Canada – the highest civic honour a Canadian can achieve.

Mr. Ménard is a director of WestJet, Claridge Inc., Stingray Digital, and Léger Marketing. He also serves as a director for the Montreal Symphony Orchestra, the Montreal Alouettes, the Institute for Research on Public Policy, the Trudeau Foundation, the Gairdner Foundation, the Macdonald Stewart Foundation, the Mobilys Foundation and the Junior Achievement Canada Foundation.

As Chancellor of Concordia University, Mr. Menard is clearly a firm believer in the importance of education in creating better lives and a stronger society. He  has championed the cause of student retention and success by authoring books on the subject and establishing the Groupe d’action sur la persévérance et la réussite scolaires. Mr. Menard is also Chair of Youth Fusion, an award-winning, non-partisan charity that establishes innovative partnerships between high schools and universities.

A member of the Task Force on Competitiveness, Productivity and Economic Progress of the Rotman School of Management at the University of Toronto, Mr. Ménard is a past Chair of Hydro-Québec, the Investment Dealers Association of Canada and the Task Force on the Sustainability of the Québec Health Care and Social Services System.

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26
Sep 2013
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StewartGarrows400EN

Will enhanced stem cells mend broken hearts?

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The unveiling of a clinical trial to test the use of genetically enhanced stem cells to rebuild badly damaged hearts captured major media attention in early September.…

The unveiling of a clinical trial to test the use of genetically enhanced stem cells to rebuild badly damaged hearts captured major media attention in early September.

CBC News, the Sun and Postmedia newspapers all called the trial “groundbreaking” and gave it prominent play. CTV  called it a “world-first clinical trial.” The Globe and Mail  coverage was somewhat more restrained but went into fine detail to explain how the patient’s own blood stem cells are enhanced with a gene called endothelial nitric oxide synthase (eNOS) that is then infused into the heart at the site of the damage.

It didn’t hurt that the Ottawa Hospital Research Institute, where Principal Investigator Dr. Duncan Stewart is CEO and Scientific Director, was able to put a gentle human face on complicated science by presenting Patient No. 1. Sixty-eight-year-old Harriet Garrow of Cornwall, Ontario suffered a major, heart-stopping myocardial infarction in July.  Holding hands with her husband Peter Garrow, she was amiable, articulate and authentic.  Reporting the news Sept. 10, the Aboriginal Peoples Television Network  highlighted her heritage, headlining its story “Mohawk woman in centre of ground breaking medical treatment.”

This is a double-blind study – meaning neither the investigators nor the 100 participants in Ottawa, Montreal and Toronto will know who received the souped-up stem cells or the comparative controls of ordinary stem cells or placebos until after the results are in. That doesn’t matter to Mrs. Garrow, who, at the very least, is getting the best of current cardiac care. “I am thrilled to play a part in this research that could help people like me in the future and, who knows, perhaps even my children and grandchildren,” she said in the OHRI’s media release.

A decade of work

Investigators will start analyzing the results after Patient No. 100 has been enrolled and treated – more than two years from now. By that time, Dr. Stewart will have put 10 years into the project he originally started at St. Michael’s Hospital in Toronto.

But things could happen quickly after that.

“Most major medical centres in Canada and the United States have the capacity to do this kind of cell manufacturing, “ says Dr. Stewart. “So, if we allow ourselves to dream a bit, that this really is a very positive trial with major improvements, I think it could be adopted quite quickly.”

The implications – in terms of thousands of lives that could be saved and millions of dollars in health care costs avoided – are immense. About 70,000 Canadians have heart attacks every year. Dr. Stewart estimates that about one-third of those, around 23,000, suffer damage severe enough to require this level of intervention.

“This segment of the infarct population is one that’s going to cost an awful lot of money because before they die they are going to develop heart failure. They’re going to be having multiple prolonged hospital admissions and require implantation of defibrillators and are going to have all kinds of other treatments that cost the system a lot of money.”

Other trials using ordinary stem cells have shown some positive effect on repairing heart tissue, but nothing that would spark widespread change in how heart attack patients are treated. The difference here is these stem cells have rejuvenated with eNOS to do a more effective repair job.

“It’s always been our view that getting the most robust therapy requires some manipulation of the cells, particularly when you’re using the patient’s own cells,” says Dr. Stewart. “The cells are the same age as the patient, which is usually 60 or 70 years old, and they have been exposed to the same factors that produced heart disease in the first place. We know they don’t work well. But if we can recover the activity of these cells we’re going to get more benefit.”

It all depends, of course, on The Big If: If it works.

Given the rigorous controls and criteria included in the clinical trial,  the answer should be obvious within three years.

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23
Sep 2013
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Norman Iscove

Quietly opening up a new frontier to fight cancer

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Just a few weeks ago, when most of us were focused on soaking up the last rays of summer sun, a new development in how stem cells renew themselves didn’t see much light of day, media-wise.…

Just a few weeks ago, when most of us were focused on soaking up the last rays of summer sun, a new development in how stem cells renew themselves didn’t see much light of day, media-wise. It should have.

Dr. Norman Iscove, a senior scientist at the Princess Margaret Cancer Centre whose pedigree traces back to pioneering bone marrow transplant efforts led by Dr. Ernest McCulloch in 1970, has quietly opened up a new frontier. One that has huge implications for cancer.

After years of work, the lion’s share of which was done by postdoctoral fellow Dr. Catherine Frelin, Dr. Iscove’s team was able to show that a gene called GATA3 plays a key role in the rate at which blood stem cells renew themselves.  They found that by tinkering with it they could get stem cells to up their self-renewal rate and make many more stem cells.

In a practical sense, this discovery could help address the shortage of stem cells for transplantation. If, by interfering with GATA3, scientists could ramp up stem cell production, doctors could then do more bone marrow transplants and save more lives.

That kind of application, however, is likely a long way off. The GATA3 findings, published in Nature Immunology, are based on work with mice – not people. “I can’t even begin to predict it,” says Dr. Iscove.  “Before knowing whether it’s playing the same role in human stem cell self-renewal, it’s too soon to say.”

But there is something more fundamental to consider here. Something that has much larger implications down the road.

“We know that stem cells can be preprogrammed in terms of longevity,” says Dr. Iscove. “There are stem cells we can purify completely that will reconstitute almost permanently. But there are others that sometime after eight weeks will begin to fail and the grafts will regress. Both of them are genuine stem cells. Both of them are capable of pumping out billions of cells every day. But one is preprogrammed to quit.  We now think that GATA3 is a key player in reprogramming the permanent stem cell to become a transient stem cell.”

Dr. Iscove believes that understanding the differences between permanent and transient stem cells is absolutely central to understanding how cancer develops.

“Cancer cells have permanence in terms of growth,” he says. “They don’t quit. They keep going. That’s why they’re dangerous.”

Viewed this way, the potential application of the GATA3 discovery is far beyond simply improving the ability to scale up the production of progenitor cells. It could be the key to shutting down cancer stem cells.

“It’s part of the puzzle of understanding permanence in stem cell renewal,” says Dr. Iscove. “How is that done and how do you break it?” The answer won’t be found anytime soon.

As said, Dr. Iscove has opened up a frontier. He and others must now explore it.

That, at the very least, is exciting.

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06
Sep 2013
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Scientists focus on curing blindness

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Want to see the future of stem cell science?  Look in the mirror.

See the retina – the thin black line outside the iris?…

Want to see the future of stem cell science?  Look in the mirror.

See the retina – the thin black line outside the iris? Those are retinal pigment epithelial (RPE) cells.  And that’s where the stem cell revolution in new treatments likely will begin.

Outstanding advances in treating leukemia, multiple myeloma and other blood-borne cancers notwithstanding, stem cells have yet to deliver the kind of treatments and cures many had hoped would be available by now. That is soon to change. Not in the blink of an eye, but certainly over the next few years.

“I think that blindness is going to be the first disease cured using pluripotent cells,” says Dr. Derek van der Kooy of the University of Toronto.

Dr. van der Kooy, whose team discovered retinal stem cells 13 years ago, bases his prediction on the fact that the retina is an easy target.

“It’s well laminated and there is this fantastic sub retinal space where you can inject the cells perfectly, exactly where they are supposed to go,” says Dr. van der Kooy. “You can actually see what you’re doing – you can look in the eye and see where you’re injecting the cells. With the heart or the brain, you can’t see where they (the stem-cell-derived transplant cells) are going. Also, it’s an incredibly sensitive assay to see whether they work or not: you can see whether vision improves.”

Dr. van der Kooy’s comments come in the wake of Japan’s announcement that it has approved the world’s first human tests using induced pluripotent stem (iPS) cells. They will be used to produce RPE cells to treat age-related macular degeneration.

Japan’s Dr. Shinya Yamanaka first demonstrated how to create iPs cells in 2006 (in mice) and 2007 (in humans).  Essentially, he came up with a process to take adult skin cells and induce them into becoming pluripotent (capable of differentiating into any cell the body needs) much like human embryonic stem cells. It was an amazing feat for which he won the 2012 Nobel Prize in Physiology or Medicine.

The discovery of iPS cells created a whole new source of pluripotent stem cells and, perhaps more significantly, got around ethical concerns about destroying embryos left over from in vitro fertilization to create embryonic stem cell lines.

But there was a problem. Dr. Yamanaka‘s original method used viruses in the reprogramming process, creating a risk of causing mutations and triggering disease.  Other researchers, notably Dr. Andras Nagy at the Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital in Toronto, have since devised other, non-viral ways of creating the cells to avoid that risk.

Japan invests $1 billion in iPS cells

Clearly, Japan thinks any risk is now negligible. The Wall Street Journal reported in late June that Japan has committed more than $1 billion over the next 10 years to advance iPS cell research and develop clinical applications. The age-related macular degeneration trial – involving just six patients – represents, the WSJ reports, “a big step forward [for Japan] in the race to develop stem-cell therapies.”

Dr. van der Kooy, however, points out that an American company, Advanced Cell Technologies, is already conducting clinical trials to test the safety of RPE cells derived from embryonic stem cells as a therapy for age-related macular degeneration and Stargardt disease (a juvenile form of the condition).

“It is the very first time that people have used iPS cells to try to treat a disease in humans, but conceptually it’s not that different than the ACT trial going on in the States right now,” says Dr van der Kooy. “And there are two other embryonic-stem-cell-derived trials that are going to start: another one in California and one in England. All four will be essentially the same type of trial – attempts to make RPE cells from pluripotent human cells for either macular degeneration or Stargardt’s.”

There is also a potentially crucial Canadian connection to this story.  Dr. Molly Shoichet, a bioengineer and colleague of Dr. van der Kooy at the University of Toronto, has developed a stem cell delivery system that uses a minimally invasive and biodegradable gel called HAMC (pronounced “hammock”) to deliver the progenitor cells to the retina.

“We’ve seen a pro-survival effect in the lab tests and in animal models,” says Dr. Shoichet. “The cells survive better when we deliver them with the gel and they integrate better in the retina.”

So the race is on to cure blindness caused by macular degeneration using with iPS cells and embryonic stem cells. “When you think about it, it’s the general argument for stem cell biology,” says Dr. van der Kooy. “Once cells have degenerated, the only way you’re going to improve them is replace the cells you’re missing.”

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07
Aug 2013
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Snipped Slamon and Mak

Not an easy job, but the demand is there

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Welcome to the first instalment of the Stem Cell NewsDesk, the Foundation’s attempt to help Canadians better understand where a “breakthrough” fits on the research lab-to-clinic continuum.…

Welcome to the first instalment of the Stem Cell NewsDesk, the Foundation’s attempt to help Canadians better understand where a “breakthrough” fits on the research lab-to-clinic continuum.

Essentially, the aim of NewsDesk is to try to answer one question: how does [insert news-making development/discovery/breakthrough here] contribute to finding a treatment or a cure for a currently untreatable or incurable disease?  The idea is not to hype stem cell science but to provide realistic reports on developments as they occur.

It won’t be easy. Stem cell science is complicated and it can be hard to decipher whether a discovery represents a monumental leap forward or is just an incremental improvement in understanding how stem cells function. Sometimes it is obvious, as with Dr. Shinya Yamanaka’s 2006 Nobel-winning discovery of how to make embryonic-like stem cells from almost any cell in the body – cells we now call induced pluripotent stem cells. Sometimes it’s not. Remember that the first demonstration of the unique properties of stem cells 50 years ago flew in under the radar.

In email correspondence, Dr. Connie Eaves, a Vancouver-based researcher whose team was the first to isolate breast stem cells, shared her thoughts on why this is such a challenge:

  • Every ‘new’ piece of information about how cells work and how their behaviour can be predictably manipulated is potentially a breakthrough – but it may take years to understand whether/when/where/or for what that will be true. So, making a fast judgment is rarely possible.
  • Current efforts use unknowns (new molecules with an experimental rationale) to treat unknowns (human tumours we don’t understand).
  • Clinically, an improvement of long-term survival from 5% to 15% would be considered a big advance. But if you were an affected patient, you might not see it that way, as overall your survival chances would still be pretty bad.
  •  What is useful clinically requires a controlled trial and this usually takes a long time (10 years) and the result may appear sort of boring by the time the answers are all in.

Case in point: the ‘sharpshooter’ story

Dr. Eaves is part of the 100-person team led by Princess Margaret Cancer Centre’s Dr. Tak Mak and Dr. Denis Slamon, (pictured at right) of the University of California, Los Angeles that made headlines in mid-June by announcing they had developed a new kind of “sharpshooter” anti-cancer drug.  Given the excellent track record of the two scientists – Dr. Mak revolutionized how scientists think about the human immune system by cloning the T-Cell receptor and Dr. Slamon developed the breast cancer drug Herceptin – it’s not surprising the announcement garnered major media attention.

As the Toronto Star explained, the new drug, which has been tested on mice for ovarian, breast, pancreas, lung and colon cancer is called a sharpshooter because it goes after a specific enzyme to shut down cancer.  Unlike chemotherapy, which can kill healthy, quick-replicating cells, the drug, called CFI-400945, takes aim only at the cancer cells.

On CTV’s Canada AM, host Bev Thompson described it as “being hailed as a major breakthrough in cancer research” and said while “we’ve talked about breakthroughs before … this seems like a cut above.”

In the Globe and Mail, however, Canada’s leading health writer André Picard, pointed out that CFI-400945, has “not been tested on a single person” and that “even in a best-case scenario” a new cancer drug “is at least a decade away.”

As excited as they were, the Princess Margaret researchers also urged patience. On that Canada AM segment, Dr. Philippe Bedard explained that the three-phase clinical trial process is a marathon, not a sprint, stressing that there is a long road ahead and it “can take many years.”

So where does that leave cancer patients?

Officials at Princess Margaret say there has been lots of interest from people who want the new drug. That will take some time: Health Canada approved CFI-400945 for use in human trials in mid-July. Next, it goes before the University Health Network’s Research Ethics Board for approval. A trial involving a small number of patients to see if CFI-400945 is safe – likely will begin in November.

So why did Princess Margaret bang the drum so loudly at such an early stage? The sharpshooter announcement actually came from The Princess Margaret Cancer Foundation to make donors aware of the potential advances that are critically dependent on the funding support that their donations provide. Makes sense:  Canadians support medical research through their charitable donations as well as through their taxes and want to know how their investments are doing.

No quick fixes

But the reaction shows that there is a real and growing need for a resource to help people understand how a treatment may have an impact on them. As stem cell research moves closer to providing new treatments, people will want to know more.

NewsDesk hopes to help in this. Again, not an easy task. And there will be lots of cautions and caveats attached to our discussions of breakthroughs.  Because the reality is: there are no quick fixes or magic bullets. But progress is being made – almost every day.

So let’s go back to Dr. Eaves, who is a member of the Foundation’s Science Leadership Council, and her thoughts on the sharpshooter announcement:

“The Tak Mak result looks very exciting in the experimental models studied to date. But there is not much history yet to know how these will correlate with patient outcomes. I can’t say much more than that and don’t think anyone can at this early stage.”

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