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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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04
Jun 2013
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Moving forward, in a big way

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The Canadian Stem Cell Foundation is on the move – in more ways than one.

After two years of operating out of the Stem Cell Network offices at the Ottawa Hospital, the Foundation is now in new quarters at 6 Gurdwara Road in South Ottawa and a satellite office on Spadina Road in the heart of Toronto.…

The Canadian Stem Cell Foundation is on the move – in more ways than one.

After two years of operating out of the Stem Cell Network offices at the Ottawa Hospital, the Foundation is now in new quarters at 6 Gurdwara Road in South Ottawa and a satellite office on Spadina Road in the heart of Toronto.

New project

The new space is necessary to accommodate exciting new projects the Foundation is rolling out First up is a completely redesigned website with a bold theme: Help Us, Help Stem Cells Help You. Its centrepiece attraction is Toward Treatments – patient-focused summaries of what stem cell researchers are doing in the battle against 14 currently incurable diseases, such as Multiple Sclerosis and Parkinson’s disease.  Prepared in partnership with the Stem Cell Network, each summary is as authoritative as it is accessible, written in reader-friendly language that makes complicated science easily comprehensible.

Stem Cell NewsDesk

We expect to have the site up and running in the summer and will be adding to it as we build for a major fall launch when another much-needed feature will be ready to go: Stem Cell NewsDesk will provide timely and realistic assessments of advances in research that the mainstream media are highlighting, and shine a light on important work that may be going overlooked.

The idea is to give Canadians a clear understanding of the difference between an incremental advance and a major accomplishment. We anticipate the NewDesk will be the go-to place for fair and balanced reportage of the progress stem cells science is making. Watch for it this fall.

A Canadian Strategy

But that is just a starting point.

The Foundation’s major undertaking over the next two years will be the crafting and implementation of the Canadian Stem Cell Strategy to guide the progress of research and development over the next 15 to 20 years. Wheels are already turning. The Foundation’s formidable Science Leadership Council is the framework for the strategy.  We are now recruiting some of the world’s leading thinkers in stem cell science and its application to join a blue-ribbon panel of international experts to provide the global context required to shape the strategy.  And we have begun consulting with Canada’s entrepreneurial and philanthropic leaders to get their input— and commitment – to help move the science safely and quickly forward.

The potential of stem cell science to treat diseases and ease suffering is immense.  We believe stem cell science is now at a tipping point – a time when potential solutions are on the verge of becoming real ones. The Canadian Stem Cell Foundation is moving forward to help make that happen.

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