Dr. James Shapiro, the man who perfected the islet cell transplant to cure type 1 diabetes, is evolving his groundbreaking research by working on a method of implanting insulin-producing cells under a person’s skin to try and stamp out the condition once and for all.
“We have cured diabetes in mice 91 percent of the time we’ve done this procedure,” says Dr. Shapiro, Canada Research Chair in Transplantation Surgery and Regenerative Medicine in the University of Alberta’s Faculty of Medicine & Dentistry.
The procedure involves implanting insulin-producing islet cells under a patient’s skin. According to the theory behind the procedure, once implanted the cells essentially take root and produce insulin in the same way as islet cells do in the pancreas of a person without diabetes. The manner in which the cells are transplanted under the skin however, is quite novel.
Implanting islet cells, or any cells, under the skin and setting them free to multiply and/or be productive has long stood as a medical challenge because the required network of blood vessels allowing the cells to circulate among the body’s systems is lacking. Shapiro and his team solved this seemingly vexing problem in a simple way.
In the article, “A prevascularized subcutaneous device-less site for islet and cellular transplantation,” announcing the results of the study and published in the journal Nature, Shapiro and his colleagues describe the implantation procedure into a “prevascularized, subcutaneous site created by temporary placement of a medically approved vascular access catheter.”
In plainer words, Shapiro put a tube under the skin to grow blood vessels.
“We inserted a nylon, plastic, five-inch catheter under the skin for a few weeks,” Shapiro says. “This induced the growth of a network of blood vessels at the site. We removed the catheter [hence the “device-less” aspect of the procedure] and implanted the cells.”
This latest innovation marks a possible improvement over the Edmonton Protocol, Shapiro’s previously heralded procedure for successfully implanting islet cells into type 1 diabetics.
Developed at the University of Alberta, in Edmonton, the Edmonton Protocol involved harvesting islet cells from cadaver pancreases and implanting them into a subject’s liver. After transplantation, subjects undertake a regime of immunosuppression similar to those who receive an organ transplant, to keep the body from rejecting the cells.
While revolutionary when the procedure was developed in the 1990s and first reported in 2000, by 2010 it was apparent that most of the subjects who received islet cell transplantation had to begin taking insulin again a year after they received the transplant.
Aside from the disappointing long-term success rate, islet cell transplantation using the Edmonton Protocol had other drawbacks. The first is that human islet cells are very expensive and difficult to acquire because they come from donor pancreases and, in many cases, subjects who receive transplants need islet cells from multiple donors. Another problem, according to Shapiro, is that “When we put islets in the liver, most of them get destroyed in a matter of minutes to hours, and we don’t have a very good way to stop that.” Additionally, the immunosuppression regimen required not only causes sometimes debilitating side effects unrelated to diabetes but, according to some researchers, may harm the islet cells over time.
Shapiro, however, doesn’t see the Edmonton Protocol as a step back, but as a step forward when placed in the larger context of efforts to cure type 1 diabetes.
“When we try something new it’s important to realize that it’s not finalized,” he says. “Everything we do is a step toward an answer. Some of those are leaps, and some are baby steps, but they all move us forward.”
Knowing that the Edmonton Protocol was only a step on the trail, and not the end of the line, is what led Shapiro to develop the device-less method for implanting islet cells.
“I woke up one day 12 years ago wondering if there was a better place to place islet cells in the human body,” Shapiro says. “I thought about how vascular tissue forms on sponges left in patients after surgery. And that led to a lot of experimentation.”
Shapiro and his team worked with a whole series of tubes trying to entice blood vessel growth, and kept trying new ones until they found an answer.
While the new procedure represents significant progress in curing, or improving the treatment of type 1 diabetes, it also holds out benefits for people suffering from other conditions.
“This exciting new approach doesn’t have to be limited to diabetes,” Shapiro said in a University of Alberta news release. “For any area of regenerative medicine that requires replacing old cells with new—and there’s lots of different disease states where there’s just one gene defect that could be corrected by a cell transplant—this opens up an incredible future possibility for successful engraftment beneath the skin.”