Canadian scientists use stem cells to reverse diabetes in mice

VANCOUVER — In a world’s first, University of B.C. scientists have used human embryonic stem cell transplants to reverse diabetes in mice.

A 13-member team, whose work was published Wednesday in the journal Diabetes, showed that as the stem cells matured into insulin-secreting cells (beta-cells in the pancreas), a few dozen diabetic mice were weaned gradually off insulin over a period of months.

The study, which cost at least $500,000, was funded by the Canadian Institutes of Health Research, the Stem Cell Network of Canada, Stem Cell Technologies of Vancouver, the Juvenile Diabetes Research Foundation and the Michael Smith Foundation of Health Research. About half the research team was comprised of scientists from the New Jersey private research and development arm (BetaLogics Venture) of Janssen Pharmaceuticals.

“It took about four to five months for the (stem) cells to become functional in our experiments and the mice were able to maintain good blood glucose levels even when fed a high-glucose diet,” said lead author Timothy Kieffer, a UBC professor in the department of cellular and physiological sciences.

Type 1 — otherwise known as juvenile diabetes — is an autoimmune disease in which a patient’s immune system kills off insulin-producing cells in the pancreas. Typically, patients must inject themselves with insulin or use insulin pumps to control their blood glucose levels.

While pancreatic islet cell transplantation — pioneered at the University of Alberta several years ago — has been shown to be an effective way of reducing dependence on insulin injections, such treatments are costly and cumbersome since they require cells culled from dead bodies; such cells are always in short supply. As well, islet cell transplant patients must forever take anti-rejection drugs that can cause organ damage.

Although the research showed that stem cells have great potential as a diabetes cure, it also revealed there are still a few pitfalls to overcome before agencies like the Food and Drug Administration in the United States or Health Canada approve such a therapy. Some mice developed bone or cartilage growths in areas where the cells were inserted, an unacceptable side-effect that future experiments must resolve.

Another obstacle is that the mice used in the study weren’t typical; they were a special strain, bred to be immuno-compromised so they wouldn’t reject the human cells as foreign invaders. Studies are continuing at UBC, in many more mice, to determine the feasibility of encapsulating stem cells in a membrane material that won’t be recognized as a foreign body and rejected.

Kieffer said he’s extremely encouraged by the fact that the mice not only were weaned off their need for insulin but also lived well and long, even though they were bred to be immune-deficient. Still, he said, researchers must find ways to fine-tune the approach so that cells don’t evolve into something other than what’s desired.

In the early stages of the experiment, some mice developed fluid-filled cysts, a problem that was rectified in the laboratory with a cell culture medium change.

“The fact that we saw cartilage-like cells means that we failed to restrict for only desirable cells and that proves the potential risks of this approach. We need to ensure that we’re getting only what we want (insulin-producing cells) and that may be done by improving the cultivation and the recipe or by purifying the cells,” Kieffer said.