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Stem cells beat diabetes in mice

19 Sep, 2012

Scientists have shown that human stem cell transplants can successfully restore insulin production and reverse diabetes in mice.

This exciting discovery by scientists from the University of British Columbia (UBC) and New Jersey-based BetaLogics, a division of Janssen Research & Development, paves the way for a breakthrough treatment for diabetes sufferers around the world.

Diabetes in New Zealand

In New Zealand, type 1 or type 2 diabetes affects some 208 000 people. According to Diabetes New Zealand, 50 more people are diagnosed with the chronic debilitating disease every day. Diabetes is diagnosed when a person has too much glucose (sugar) in the blood, because the pancreas is not making enough insulin. The insulin helps the body absorb sugar and use it for energy. Type 1 sufferers are people who make little or no insulin, as their immune system malfunctions and kills off their insulin-producing cells in the pancreas. They are dependent on insulin injections. Type 2 sufferers are people who have a sluggish pancreas, almost always as a result of being overweight. Type 2 diabetes can be treated with weight loss and regular physical activity, but if this is not successful patients can eventually require insulin injections. Continuing high blood sugar levels can eventually lead to blindness, heart attack, stroke, nerve damage and kidney failure.

There is currently no widely available cure for type 1 diabetes. Experimental transplants of healthy pancreatic cells from human donors have shown to be effective. However, this treatment is severely limited by the availability of donors and means a lifetime of anti-rejection drugs.

How the human stem cell transplants worked in mice

The new research by the Canadian and American team involved transplanting stem cells under the left kidney of dozens of diabetic mice. The stem cells then matured into insulin-secreting, pancreatic beta-cells, which could automatically sense blood sugar levels to release the right amount of insulin. (This is called the feedback loop, where insulin levels rise or fall based on blood glucose levels.) This allowed the mice to be gradually weaned off insulin injections over 3–4 months – a procedure designed to mimic human clinical conditions. The mice were able to maintain healthy blood sugar levels even when being fed large quantities of sugar. Transplanted cells removed from the mice after several months had all the markings of normal insulin-producing pancreatic cells. Essentially, the mice were cured of their type 1 diabetes.

More research before human trials

Lead researcher Professor Timothy Kieffer, a professor in the Department of Cellular and Physiological Sciences at UBC, said in a press release, “We are very excited by these findings, but additional research is needed before this approach can be tested clinically in humans. The studies were performed in diabetic mice that lacked a properly functioning immune system that would otherwise have rejected the cells. We now need to identify a suitable way of protecting the cells from immune attack so that the transplant can ultimately be performed in the absence of any immunosuppression.”

In addition, the process still needs to be further refined. A few of the mice developed bone or cartilage in areas where the cells were transplanted. In various media interviews, Professor Kieffer explained that, as the researchers also saw cartilage-like cells in some mice, they had failed to restrict for only desirable cells – showing the potential risks of this approach. Further research by the team aims to improve the cultivation techniques and the purity of the initial stem cell batches.

The research 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 for Health Research.

The study was published in the journal Diabetes.

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