Diabetes researchers are reporting early success in a first-in-humans clinical trial to test whether pancreatic cells grown from stem cells can be safely implanted and begin to produce insulin.
The team reported on their proof of concept and safety study in a newly published paper in the journal Cell Reports Medicine.
Of 17 patients who received implants, 35 percent showed signs in their blood of insulin production after meals within six months of the implant, and 63 percent had evidence of insulin production inside the implant devices when they were removed after a year.
“This is a very positive finding,” said first author James Shapiro, professor of surgery, medicine and surgical oncology in the Faculty of Medicine & Dentistry and Canada Research Chair in Transplant Surgery and Regenerative Medicine.
“It’s not the endgame, but it’s a big milestone along the road to success, demonstrating that stem cell-derived islet therapies are safe, and can begin to show some signal of efficacy in patients in the clinic,” said Shapiro, who is also a member of the Alberta Diabetes Institute.
“Remarkable and exciting”
Shapiro led the team that developed the Edmonton Protocol in the 1990s, a process that allows successful transplantation of donated insulin-producing islet cells into the livers of people with Type 1 diabetes. Most are freed from the need for daily insulin injections, but they continue to need anti-rejection drugs, which can have negative side-effects such as an increased risk of cancer and kidney damage. Also, the number of donated islet cells available is limited.
The ultimate goal of the current research is to develop an unlimited supply of islet cells that can be safely transplanted without the need for anti-rejection drugs, said Shapiro, who is also director of liver, living donor and islet transplant programs for Alberta Health Services and a fellow of the Royal Society of Canada.
In the trial, adult diabetes patients at six centres in Canada, the United States, and Europe received implants of several small permeable devices filled with millions of cells each. The cells were derived from stem cells, then chemically transformed into stem cells programmed to become islet cells.
Some of the implants, the size of a postage stamp, were put in the forearm, while larger devices about half the size of a credit card were implanted in the abdominal wall. All the patients took immunosuppressant drugs.
“The idea of the multiple small devices was so that we could remove them at different time points to see — are the cells surviving? Are they working? And are they doing what they’re supposed to do?” explained Shapiro, noting that no safety concerns were raised.
“It is remarkable and exciting that the patients tolerated these devices and the surgeries so well,” he said.
Shapiro said that while ascertaining safety was the main goal of this phase of the trial, at least one patient who had 10 devices implanted was able to significantly reduce her insulin dose, indicating the potential effectiveness of the treatment.
The next step for the research will be to determine how many stem cell-derived pancreatic cells are needed for transplant to optimize insulin production in patients with both Type 1 and Type 2 diabetes.
A trial set to start in Canada in early 2022 will see researchers transplant pancreatic cells that have been genetically engineered to remove the targets that are normally attacked by the immune system of people with Type 1 diabetes.
“The idea is to transplant these quiet or stealthy cells without any of the anti-rejection drugs, which would be a huge advance,” said Shapiro.
Final laps of a marathon
Shapiro, who began his search for improved diabetes treatments 38 years ago, likens the intensive research required to a marathon.
“We’ve seen a lot of advances in the last 100 years since the Canadian discovery of insulin,” he said. “The race isn’t over yet, but we’re on our last laps and I really do believe that we can cross that ribbon.”
“Cell-based therapies have the promise to deliver something far better than insulin therapy,” Shapiro said.
Source: University of Alberta
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