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The discovery of insulin-creating multipotent cells in the pancreas brings stem cell science another step closer to defeating Type 1 diabetes.

A team of Canadian scientists has taken a big step forward in the journey to find a cell-based therapy to defeat diabetes.

Work at the University of Toronto, by Drs. Raewyn Seaberg, Simon Smukler, and Derek van der Kooy and team members across the country, has identified what has eluded scientists until now: a single cell in the pancreas capable of creating insulin-producing beta cells.

The findings, to be published in the September 2004 edition of Nature Biotechnology, represent a fresh new hope for diabetics in Canada and across the world who must undergo regular injections of insulin to compensate for defective pancreatic islet cells that regulate the body's blood sugar levels.

"This represents a potential cure for a deadly disease," says Dr. van der Kooy. "It wouldn't have happened – at least it wouldn't have happened in Canada – without the Stem Cell Network. This is an example of bringing together people with different expertise. And it worked out wonderfully."

In fact, the discovery could be a case study in cross-Canada collaboration. Dr. van der Kooy used "essentially the same assay" for identifying neural stem cells developed by Samuel Weiss at the University of Calgary. Because Dr. van der Kooy was unfamiliar with pancreatic cells (his expertise is retinal and neural stem cells), Timothy Kieffer, now at the University of British Columbia in Vancouver, and Gregory Korbutt, a University of Alberta professor who worked on the Edmonton Protocol for islet transplants, provided the needed help.

"Their work was spectacular," said Dr. van der Kooy. "We had the techniques available, but we simply didn't have any background in studying pancreases. They provided the tissue that allowed us to proceed."

The discovery offers considerable new hope, as it contradicts a recently published paper that suggested no such cell exists in the pancreas.

"It's very exciting," says Joel F. Habener, Professor of Medicine at Harvard Medical School and Associate Physician at Massachusetts General Hospital. "An earlier paper in Nature said, essentially, there are no stem cells in the pancreas. So this is a highly important paper in the field. This paper shows there is a rare cell that has the property to be a precursor, be multipotent, and create insulin cells."

Many researchers have claimed there are adult stem cells in the pancreas, says Dr. van der Kooy. "They saw some new pancreatic cells being generated, but they didn't know which cells were doing it. We've shown that a single cell cultured from a pancreas can produce all the cells in the pancreas, including insulin-producing ones."

Dr. van der Kooy is careful to call the cell "a multipotent precursor cell" and not a stem cell. "If a stem cell is defined by its ability to proliferate and produce all the cells, then we've done that. But to truly show it's a stem cell, we have to show it can renew itself. We haven't shown that yet. We're working on it."

The discovery builds on a proud history of diabetes research in Canada, from the 1920s discovery of insulin by Frederick Banting and Charles Best, to the development of the Edmonton Protocol for islet transplantation in 2000 by University of Alberta researchers, which has freed some diabetics from insulin injections. Given that donor organs used in the protocol are in such short supply, this discovery could be a key to the future treatment of diabetes.

"If this process can be replicated in human tissue, and scaled up, it could provide a means of making the islet transplant protocol that was developed in Edmonton more widely available as a therapy for Type 1 (juvenile) diabetes," says Dr. Kieffer.

The next step, says Dr. van der Kooy, will be testing the cells in mice to see if they can rescue diabetes, a step that would bring them ever closer to a cure.

Robert R. Hindle, Chairman of the Board of the Juvenile Diabetes Research Foundation of Canada, calls the discovery "a tremendously encouraging step forward for everyone affected by juvenile diabetes. This is a very tangible demonstration of how the SCN has rapidly moved forward stem cell and stem cell-related research, which offers a wide array of therapeutic potential. At the same time, this discovery shows how rapidly specially focused research can zone in on the target. The SCN has created a unique forum to permit widespread multidisciplinary research across the world. It is worth noting that, once again, a major step forward in diabetes research has occurred in Canada."

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