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Research at U of S |
 Skin derived precursor cells. (photo courtesy Freda Miller) |
Hope or Hype?:
The Realities of Stem Cell Research
by Michael Robin
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Expectations can get raised beyond what is actually achievable in the near future,” says James Till, currently a professor emeritus at the Ontario Cancer Institute in Toronto.
Freda Miller, a senior scientist at Sick Kids Hospital in Toronto, concedes the possibilities are truly exciting – a topical cream that would allow burn victims to re-grow their own skin, for example, or a cure that would allow paraplegics to walk again. But these are “dream situations,” and the first applications are apt to be more modest.
“In the shorter term, in the next 10 years or so, the application might be something like helping bone healing or cartilage repair – things that are a bit easier to go in and surgically repair,” she says.
Stem cell research was born in the 1960s when Till and collaborator Ernest McCulloch first revealed to the world that the body contained precursor cells capable of producing all three constituents of blood: white blood cells, platelets, and red blood cells.
Till’s research career began at the U of S in the 1950s just after Harold Johns and his team had set up the first cobalt-60 radiation therapy machine for cancer treatment.
Johns, Till’s advisor for his Master’s degree, found a biophysics program at Yale that matched the young scientist’s interest: the effect of radiation on living cells. Later, after moving to the new Ontario Cancer Institute, Johns offered Till a job.
Here, Till met McCulloch, a physician and researcher who wanted to try experiments on irradiating mice and transplanting bone marrow. He needed a biophysicist to make it happen and Till volunteered, forming a lifetime friendship and a collaboration that would last two decades.
The two set up experiments where mice were exposed to a radiation dose that would kill them within a month. Then they gave them bone marrow transplants from healthy mice. The irradiated mice survived.
 James Till (left) and Ernest McCulloch were the first in the world to discover stem cells. (PhotoGraphics, University Health Network) |
“Others had shown that cells in the transplants were responsible for this spectacular result,” Till says. “But little was known about those cells.”
Zeroing in on this question involved irradiating the donor marrow at different doses to determine the radiation sensitivity of the cells that were allowing the mice to survive. It was during one of these experiments that McCulloch noticed something odd.
One Sunday, while dissecting mice that had received relatively small numbers of transplanted bone marrow cells, he found bumps on their spleens. That Monday morning, McCulloch looked for Till.
“He was waving this piece of paper, and saying, you’ve got to see this!” Till recalls.
“This” was a piece of graph paper showing that the bumps matched the bone marrow cells – the more cells transplanted, the more bumps – colonies founded by the marrow cells. Subsequent experiments showed that the colonies stemmed from cells capable of self-renewal, with the ability to differentiate into different kinds of cells. This definition of stem cells still holds true today.
“What our work showed was pretty strong support, at least in the mouse, for a multipotent stem cell,” Till says.
The discovery forged a new field of stem cell biology. In 2005, Till and McCulloch received the Lasker Award, often called“America’s Nobel,” for their work.
Today, adult stem cells have been found in the brain, eye, heart, muscle, intestines, and even fat. All are multipotent: able to differentiate into a few different cell types. There is also a type of stem cell that is pluripotent – able to differentiate into any of the body’s 200-plus tissue types. These are embryonic stem cells, formed mere days after an egg and sperm unite. Typically, such cells come from surplus embryos from in-vitro fertility treatments.
 Freda Miller. (photo courtesy Freda Miller) |
Therein lies the controversy. Under proper treatment and with a little luck, these embryos have the potential to develop into people. But since they are surplus, to be destroyed anyway, is it ethical to use them to help improve the lives of others?
Miller has found an alternative that, at least in part, circumvents this thorny issue: stem cells from adult skin.
A native of Calgary, Miller moved with her family to Saskatoon in time to pursue a BSc in biochemistry in 1979. She returned to her hometown to launch straight into a PhD in molecular biology from the University of Calgary. After completing her postdoctoral training at the Scripps Research Institute in California, she returned to Canada and a faculty research position at the University of Alberta.
Five years later, she moved to Quebec, and a research program at the Montreal Neurological Institute at McGill University that would make headlines around the world.
Miller reasoned that since skin constantly renews itself, it would be a good place to look for stem cells. Also, the skin’s deeper layer, the dermis, contains numerous receptor cells that transmit information about the outside world. As a neurobiologist, she wondered if these cells and nerve cells might have common origins.
The team isolated what they called“skin-derived precursors” – SKPs – that can differentiate into blood, fat, various types of skin tissue, and perhaps most exciting, neurons and the glial cells that support them. The research was published in 2001.
“This particular class of very potent precursors exists in adult skin tissue,” Miller says. “The stem cells that help to build the embryo into many things don’t just disappear.”
This spring, Miller was guest of honour and keynote speaker at the U of S College of Medicine for its annual Life and Health Sciences Research Conference. She told the standing-room-only crowd about her research with collaborators in Toronto that showed SKP-derived Schwann cells – a particular type of glial cell – may help heal spinal cord injuries.
Schwann cells are responsible for creating the myelin sheath around nerves, which basically acts as “insulation” around the nervous system’s “wires.” Without myelin, nerves cannot transmit their signals effectively, nor can they determine where to grow. This is a major challenge in spinal cord injuries, where nerves cannot find their way across the damage to heal the break. The result is paralysis.
When Miller and her collaborators treated paraplegic rats with SKP-derived Schwann cells, the animals regained movement in their lower extremities. Subsequent study showed the cells had produced myelin, allowing the neurons to create new connections.
The work has broad and long-term implications not only for spinal cord injuries, but for the treatment of stroke victims or even people suffering from diseases such as Parkinson’s.
And while adult stem cells can’t match the versatility of the embryonic version, they may just offer a range of exciting benefits of their own.
