Stem Cell Research Matures in Montreal Studies

Dr. Freda Miller has a vision. It is that someday she could take a bit of someone’s skin and transform its “blank slate” stem cells into brain tissue to alleviate that person’s Parkinson’s symptoms, or pancreatic cells to cure a patient’s diabetes. (No cloning necessary.)

Miller and her research team at McGill University’s Montreal Neurological Institute unveiled the first step toward that vision last week when they announced that they have discovered stem cells deep in the skin of rats and humans that can become fat, muscle or even brain cells.

The discovery, detailed in the September issue of the journal Nature Cell Biology, is a significant step in research showing that stem cells of adults--not just those found in embryos--can change into many types of tissue. If adult stem cells can be used to treat diseases, they might provide a way to sidestep the moral dilemma of whether a tiny cluster of cells from an embryo represents human life. President Bush grappled with that question this month in deciding to limit federal funding for embryonic stem cell research.

As potentially valuable as it is politically charged, stem cell research is one of the fastest-moving areas in molecular biology. A few years ago, scientists thought that adult stem cells could change only into the same class of tissue as their place of origin. Only stem cells found in the brain, according to this reasoning, could become neural cells, while only those found in bone marrow could help make blood.

In the past year and a half, however, studies have shown that these powerful cells can be coaxed into quite different fates. Stem cells found in the brain can be changed into muscle, and those in bone marrow can turn into liver cells. Unlike their embryonic counterparts, though, adult stem cells are painful to harvest and difficult to divide, and their cell lines--the sets, or colonies, derived from them--are generally short-lived.

But the stem cells found at McGill, which seem to be exceptionally versatile, are easy to generate and simple to collect--the practical beauty of the discovery is that it is only skin deep. Miller’s study is the first to claim that a single adult stem cell can give rise to two of three of the basic classes of cells in the body. The McGill lab is working to confirm that it can generate cells for all three, and preliminary results are encouraging, Miller says.

“As a scientist, you’re trained not to hope too much,” she said. “But on this project, things keep turning out well.”

Most important, in an experiment yet to be published, researchers implanted neural cells derived from skin stem cells into rat brains, where they seemed to meld well with the surrounding tissue and act like the cells around them. Next, the team will implant the cells in rat brains with simulated Parkinson’s disease to test whether they can help restore brain function.

Still, it’s a far step from rat brains to treatments that will work in human brains. Although the researchers allowed themselves champagne toasts and a quick celebration the day their article was published--after two years of checking and rechecking their results--they know this is just the beginning.

They plan to spend the next two years learning how to induce the cells to become specific types of tissue and how to control their development once they do. (A neuron derived from a skin cell, for example, needs to remain a neuron.)

Miller said the researchers also need to duplicate more of their rodent results with human cells. But the scientists are driven by the hope of bringing science closer to treatments for spinal cord injuries, juvenile diabetes, heart disease and brain disorders--treatments made from patients’ own cells.

According to Miller, the biggest limitation to working with adult stem cells is that so little is known about them. It was only two years ago that one researcher in the McGill lab, Jean Toma, asked, Why not look for stem cells in skin? The dermis is rich in different types of cells, including neural cells that sense temperature and pressure. It repairs itself quickly without losing sensation. And it’s easy to obtain samples.

The scientists decided to give one experiment a couple of months. Within a few weeks, they had the first hints that neural cells were developing from stem cells they had harvested. Then they exposed those cells to different growth cultures to coax them into becoming different types of cells--bubble-like fat cells, and the lithe cells of smooth muscle. Most significant, they produced several kinds of brain cells, including neurons, the thinking units of the brain, and glial cells, which produce the nerve fiber sheaths that can be damaged by multiple sclerosis.

To prove that all the different types were originating from a single skin stem cell, they also isolated lone cells and started over. And over. And over again. They allowed the single cells to flourish into small colonies to see how long they could keep generating. Most adult stem cell lines peter out after a short time, while their embryonic cousins, by comparison, can keep dividing indefinitely.

The lab members, alternately ecstatic and skeptical, brought in a small cake on the cell line’s 1-year “birthday.” In November, the cell line will turn 2.

“They’re still growing like crazy,” Miller said.

Though the advances made by Miller and her colleagues are coming almost on top of one another, their newly discovered stem cell is a long way from replacing the embryonic stem cell in research or therapy.

“We’re so far behind still in adult stem cells,” Miller said. “You can make more than 200 cells from an embryonic stem cell--every type of cell in a human being--and at this point, only five or six from ours. That’s a very big gap.”

Other scientists are watching their work carefully.

“Stem cell biology is important for all areas of medicine, and so we’re going to have to explore the properties of all these cells,” said Ronald McKay, a stem cell expert at the U.S. National Institutes of Health who regards the McGill discovery with cautious optimism. “What we’re likely to be going into now is a period of many claims and many ups and downs.”

A number of players, public and private, have come together in Canada to help stimulate this research. Miller’s work is funded in part by two private companies that have licensed McGill’s patents on the discovery: Curis Inc. of Cambridge, Mass., and Canada’s Aegera Therapeutics Inc. The rest of the funding comes from a combination of grants from the Christopher Reeve Paralysis Foundation and the Canadian government’s newly formed Stem Cell Network, a consortium designed to nurture pioneering work.

Spurred by recent debate in the U.S. over the limits of stem cell research, and the reported efforts of a Canadian cult known as the Raelians to start cloning humans, the Canadian government is pushing new legislation to restrict embryonic stem cell research.

Canada’s draft law is more liberal than the United States’ new policy. It would allow stem cells to be taken from embryos left over from in vitro fertilization procedures but would not tolerate the creation of embryos solely for research. As in Britain, it would permit embryos to be used only within 14 days of their creation and only with the donor’s consent.

But even scientists like Miller, who doesn’t directly use embryos or cloning in her work, are wary of interference. Miller emphasized that even if adult stem cells are all they promise to be, it is crucial that researchers still have access to embryonic stem cells for comparison.

“I don’t want people to use our work as a reason to not use embryonic stem cells,” she said. “So much of our work is based on embryonic stem cell research, I would really hate at this early point to see any of that work impeded.”