Canada Is in the Vanguard of Stem Cell Research
PETER SAUER FELT his life slipping away. In 1994, doctors diagnosed Sauer, then 59, with Parkinson's disease, a cruel brain disorder that progressively robs sufferers of the ability to move or function normally. Sauer soon retired from his job as a parts manager with Bell Canada in Toronto and returned to Prince Edward Island where, earlier, he had farmed for over two decades. "I came back to build a house on land I still owned," says Sauer. "My neighbours thought I was building myself a coffin."
Small wonder: as the disease took hold, Sauer's body shut down. His hands trembled uncontrollably. His walk became a hunched shuffle. He could no longer feed or dress himself. "I've always been terribly scared of being shunted off to a corner somewhere," he says. "That's where I was headed."
Salvation came in the form of a pioneering cell transplant program overseen by Ivar Mendez, head of neurosurgery at Queen Elizabeth II Health Sciences Centre in Halifax. Starting in 2001, Mendez began transplanting brain cells from fetal tissue into the brains of 10 Parkinson's patients who hadn't responded to other therapies. He was trying to replace the dopamine-producing cells, which spark connections in the brain, that the disease destroys. Within months, all patients showed dramatic improvements. In Sauer's case, his tremors nearly disappeared and he became independent enough to drive his car and take part in community events, including an all-night tobogganing party in February. "I've been given," says Sauer, now 70, "a new lease on life."
Mendez and his team realized that the transplant results, though gratifying, represented only one piece of a puzzle. Still to be overcome: finding enough specific fetal cells to turn such operations into a routine treatment for the 100,000 or so Canadians suffering from the disease. What Mendez needed were cells that could be culled and cultivated in vast numbers, then transplanted into the human brain to perform a specific task. What he needed were the wonder agents known as stem cells.
Mendez is now leading a nationwide research project aimed at developing stem cells from adult skin, bone marrow and brain, and training them to do on a mass scale what the fetal brain cells did for a lucky few. The production issue has been cracked: University of Calgary engineer Leo Behie has developed a bioreactor for growing human neural stem cells in the lab. "We can send him a million cells," says Mendez, "and, four weeks later, we get 300 million back." If the stem cells can be coaxed into becoming dopamine-producing cells - and steady progress is being made on that front - they'll be injected into the brain using instruments designed and patented in Halifax for the original 10 Parkinson's patients.
A handful of similar high-end research is underway in the United States and Britain. But Canada's efforts may be more focused in that Ottawa is using its funding clout to help link the work of 80 leading scientists in information-sharing, multi-city teams, something it calls the Stem Cell Network. The potential benefits extend far beyond a single disease. "I envision a time," says Mendez, "when, if you suffer a traumatic brain or spinal cord injury, you'll be rushed to the emergency room and there will be cells on hand which can be injected into the brain to repair you. It would be a routine thing."
A routine miracle is more like it. While Mendez's ER scenario is likely years - even decades - away, other breakthroughs are much closer at hand. Stem cell research projects around the world look to move into human trials within two to five years, if not sooner. Among other things, scientists are exploring the seemingly limitless potential of stem cells to repair damaged brains, spinal cords and hearts, as well as to treat a host of debilitating conditions such as diabetes, blood disorders and Alzheimer's.
For this they can thank two Canadians, Alberta-born biophysicist James Till and Toronto physician Ernest McCulloch, who first discovered the existence of stem cells in the 1960s while doing Cold War research on radiation. They seem to have started a big ball rolling. In 2002, the journal Nature Immunology identified 35 of the most significant stem cell research papers published in the last half of the 20th century; Canadians wrote almost half of them. "When it comes to stem cells, Canada is a powerhouse," says Alan Bernstein, president of the Canadian Institutes of Health Research, a federal funding agency, and a distinguished stem cell researcher in his own right. "There's some beautiful science going on here."
None of this research is without controversy, of course. In the U.S. in particular, stem cell research is a hot-button issue that has reached right to the heart of presidential campaigns. Critics argue that because any human embryo has the potential to be a living being, destroying one in the name of science is morally wrong. Proponents counter that since excess embryos are routinely discarded by in vitro fertilization programs - women undergoing IVF often have as many as eight fertilized eggs to choose from - harvesting the stem cells from unwanted eggs to advance research into life-debilitating disease is both logical and ethical.
Canada's Assisted Human Reproduction Act, passed in 2004, allows research on spare IVF embryos as long as it promises a clear benefit for human health. (The act outlaws the creation of embryos solely for research - and therapeutic cloning for any reason, though the latter is allowed in places like Britain and South Korea. And scientists in both countries just announced they had cloned human cells for research.) Still, the ongoing controversy obscures one key fact. Embryonic stem cells are the most powerful of nature's building blocks: created in the first days after conception, they can develop into any biological cell. But increasingly, researchers are looking to adult stem cells - and other similar cells present, sometimes dormant, in the mature body and brain - to get the job done. This skirts the ethical concerns over embryos. But it's where science is taking the research. It's also where Canadians are out in front of the pack.
IT'S A SLIGHT exaggeration, perhaps, to call Sam Weiss the stem cell whisperer. But when the University of Calgary neuroscientist describes his research to treat the ravages of stroke, that's what it sounds like. Working with rats, Weiss is trying to see if stem cells that reside in the brain, and which helped form the organ in the first place, can be coaxed into replacing the cells that are killed when a stroke occurs. (The death of this grey matter is what permanently robs stroke victims of muscle control, speech and memory.) "Basically," says Weiss, "what we're trying to do is tell these resident stem cells, 'Go back to your childhood, kick it into high gear, because you have to recreate what you had already created.'"
In 1992, Weiss's lab became the first to prove that adult stem cells exist in the brain. It was a finding that defied conventional wisdom, made the cover of the prestigious journal Science, and garnered headlines in nearly every major newspaper around the world. Now, Weiss is on the cusp of another breakthrough. Research shows that, after a stroke, some adult stem cells automatically head toward the site of the injury, though not in nearly enough numbers to repair the damage. By injecting the site, though, with growth factors - naturally occurring proteins produced by the body to promote new tissue - Weiss's team has found that it can boost the number of stem cells sent to the stroke area a hundredfold.
The results are remarkable. In some cases, stroke-induced rats regained the use of damaged limbs. Within two weeks, they were able, eight times out of 10, to use whichever limb was afflicted by the stroke to reach out and grasp a pellet of food. Feeding oneself is a simple act but one that human stroke victims often have enormous difficulty doing.
Weiss's work finds echoes in that of Ottawa heart scientist Lynn Megeney. Three years ago, Megeney and biologist Michael Rudnicki identified a group of cells in adult cardiac tissue that behave like stem cells. That discovery, too, went against accepted dogma. Now, Megeney leads a project aimed at luring these heart cells into performing a specific life-saving function: replacing the cardiac muscle destroyed by heart attacks.
Few organs are as unforgiving as the heart: damaged cardiac muscle, denied oxygen in the blood because of a blockage in an artery, does not regenerate or repair itself effectively. But animal studies are showing that if the right protein is injected shortly after a heart attack, heart cells will expand in number to replace dying muscle cells and reduce the size of the "infarct," or area of damage, by up to 40 per cent.
The cells Megeney is working with are not, strictly speaking, stem cells. They don't have the ability to turn themselves into a variety of cell types. But they will transform into heart muscle cells - at least in animals (Megeney figures human trials are three to five years away). At the same time, he is collaborating with University of Calgary biologist Jay Cross, who is trying to identify the factors that turn early embryonic stem cells in mice into heart muscle. Finding the human equivalent would open up the door to creating human heart muscle in the lab before injecting it back into a heart attack victim. "At this stage," says Megeney, "you can't rule one option out over another."
DIABETES is another chronic disease benefiting from this kind of research. In 1999, University of Alberta researchers developed the so-called Edmonton Protocol in which patients suffering from Type 1 or juvenile DIABETES are injected with insulin-secreting cells, known as islets, from donated human pancreases. During the first year following the procedure, 80 per cent of patients no longer need daily insulin shots and are freed from the wild blood sugar swings that threaten their lives. But the benefits seem to wear off with time.
Another limitation: two pancreases are needed from donated cadavers to harvest enough islets for one transplant. Lawrence Rosenberg, a professor of medicine at McGill University, is leading a seven-city project aimed at developing a limitless supply of insulin-producing tissue. This would also help people with Type II diabetes - the vast majority of those with the disease.
Rosenberg's team has identified two populations of cells in the adult human pancreas that can be manipulated into becoming islet cells. Within 18 months he hopes to begin transplanting these cells into animals to see if they will function as real islets. If that is successful, it is on to human trials.
At Toronto Western Hospital, stem cells are being harvested from the spinal cords of organ donors, one of only a small handful of such projects in the world. Led by neurosurgeon Charles Tator, the team has found that, in rats, transplanted stem cells can be kept alive for weeks and mature into adult-like spinal cord cells. The challenge is to see if they can effect repairs.
Even with animal studies incomplete, Tator's lab has collected nine human spinal cord specimens to lay the groundwork for eventual human trials. Implanting stem cells is one of about 15 new strategies currently in play for treating damaged spinal cords, a condition that affects some 30,000 Canadians. One includes drugs to help nerve cells sprout new connective fibres; another involves transplanting olfactory cells from the nose (which have a stem cell component) into the injured area - a procedure being performed in China on a highly experimental basis. Tator is part of a group of North American researchers trying to determine which option is best to take to human trials first, something he thinks could happen within two years. "It's unbelievable how much we've learned about the injured nervous system and how to repair it," he says. "We're very close to taking it to the next step."
Maclean's May 30, 2005