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Diabetes researcher Dr. Timothy Kieffer. (Martin Dee for The Globe and Mail)
Diabetes researcher Dr. Timothy Kieffer. (Martin Dee for The Globe and Mail)

For type 1 diabetics, stem cells may offer a future without injections Add to ...

Dr. Timothy Kieffer recalls the moment when he realized the treatment of diabetes was going to change forever.

In the late 1990s, Kieffer’s colleagues at the University of Alberta were trying to use pancreas cells from cadavers to supply diabetics with insulin – thus eliminating painful injections. While the technique wound up having problematic side effects, it inspired Keiffer and eventually led to his own breakthrough: Instead of relying on donated tissue, he thought, why not use the amazing regenerative capacity of stem cells.

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“The concept of using cells instead of needles just made so much sense to me,” says Kieffer, now a researcher and professor at the University of British Columbia.

Kieffer is part of a long line of Canadian scientists working to put an end to diabetes, which affects three million Canadians. That number is rising, due to an aging population, increasingly sedentary lifestyles and obesity rates.

Nine decades after Toronto researchers Frederick Banting and Charles Best invented the insulin injection and won a Nobel Prize, Kieffer and his colleagues are among the scientists racing toward a similar revolution in the treatment of diabetes – one that they say could make insulin injections obsolete. They are harnessing a powerful tool Banting and Best could never have imagined: human embryonic stem cells (hESCs).

As anyone who lives with diabetes knows, insulin injections are a dicey way to treat the disease. If the amount of insulin injected is too low, blood-glucose levels remain too high, leading to nerve and blood-vessel damage. Inject too much and glucose is sucked right out of the bloodstream, which can cause impaired brain function and even coma.

Dr. Laura Rosella, a scientist with Public Health Ontario, says there are two ways patients can gain from ditching the needle. “From the perspective of the patient, it improves quality of life. There’s also the potential for a dosage error. The most negative impact of that is death.”

Human embryonic stem cells are derived from human embryos and can grow and divide in the laboratory to an almost unlimited degree. They have the ability to turn into any of the 200 different cell types in the body – including the pancreatic cells that produce insulin.

While Kieffer isn’t the only scientist harnessing the power of stem cells to treat diabetes, his strategy is unique. Working with biotechnology firm BetaLogics in New Jersey, Kieffer says he and his colleagues worked to optimize the process by which hESCs are turned into pancreas cells. Next, they created a method to protect those cells so they aren’t destroyed by the immune system of the host patient after the transplant procedure. That requires a “macroencapsulation device” – a small plastic pouch measuring about one-by-two centimetres that is implanted just beneath the skin.

The pouch has room inside for a few teaspoons of cells and is made of a material permeated by microscopic holes. “Nutrients can get into the chamber, including glucose, and the insulin produced can get out of the device into the bloodstream where it is carried throughout the body to do its job,” Kieffer says. Crucially, the tiny holes in the pouch are too small to admit entry to the body’s immune cells, meaning rejection is unlikely.

Although type 1 diabetes is more rare, Kieffer’s innovation is designed for type 1 diabetics because they need supplemental insulin to survive. “While type 2 diabetics have many treatment options,” says Kieffer, “about one-third will require insulin therapy. It’s reasonable to expect a cell-based approach may be effective in these patients, too.” Research into the pouch applications for type 2 diabetics is ongoing.

This year, Kieffer’s group published a scientific paper in the journal Diabetologia showing that stem-cell-derived pancreatic cells transplanted into diabetic mice churned out enough of their own insulin to eliminate the need for injections. “We were ecstatic to see blood sugar levels eventually come down to normal levels,” says Kieffer.

The findings were greeted with cautious optimism by others in the field. “This is a very important experiment that is taking us a step closer to a potential new treatment for type 1 diabetes,” says Dr. Maria Cristina Nostro, an assistant professor in the Department of Physiology at the University of Toronto, and a world-renowned expert in stem-cell therapeutics. She warns there are still unknowns with Kieffer’s technique. It’s unclear whether the small number of cells in the “teabag” will be enough to reverse diabetes and how long those cells will survive.

“While there is still a very long way to go before human embryonic stem cells or their derivatives can be considered a viable treatment for diabetes, any forward progress is welcome at this stage,” added Dr. James Johnson, an associate professor of medicine at UBC who has collaborated with Kieffer on other projects.

It could be another decade before clinical trials are complete and the effectiveness of Kieffer’s stem-cell therapy is fully tested. Kieffer agrees there are still hurdles to clear. “One concern with any stem-cell-based therapy is if some stem cells remain in the transplant, they may continue to proliferate, forming a tumour,” he says. However, one potential advantage of his plastic “teabag” is that “it should contain any rogue cells and is easily removed if there’s a problem.”

Despite the challenges that lie ahead, Nostro is optimistic about stem cells’ potential in the treatment of diabetes. “Translating this work to the clinic might take time,” she says, “but so far these exciting findings are taking us closer to realizing our dreams.”

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