Infusing Donor Islets into Muscles: A New Direction for Islet Cell Transplants?

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After failing to live up to its early promise of becoming a cure for type 1 diabetes, the procedure of transplanting insulin-producing islet cells into a person’s body shows signs of having other applications for treating diabetes. And researchers recently have not only come up with a way to make the procedure safer and easier, but could be close to making it so there’s an unlimited supply of the cells.

This second wind for islet cell transplantation is particularly welcome news to me. In 2006 I received an islet cell transplant at the University of Virginia.

The procedure I underwent was based on the “Edmonton protocol.” It was in Canada that researchers in 2000 first successfully infused human islet cells from cadaver pancreases into a person’s portal vein leading to their liver. In that original clinical trial, seven subjects became “insulin independent,” creating hope that the grail of a cure for type 1 diabetes was at last within the grasp of science.  

For me, the promise seemed to hold out hope. Shortly after I received my transplant I was “cured” of type 1 diabetes in the sense that I was no longer taking insulin. But the honeymoon was short lived. Like the majority of subjects who received such an experimental transplant, the cells that were infused into my liver stopped working, or outright died, after a few years.

As for all such transplant recipients, the reasons the cells stopped working was a mystery. It might have been that the immunosuppression regime I was on was too harsh for the delicate cells. It could have been that the body’s immune system attacked the cells, as they did when I was first diagnosed with diabetes. It could have been that the cells just up and died for no particular reason.

The failure was more than a personal loss for me because I was typical of subjects who underwent the experimental procedure.

“This study and other reports of successful islet cell transplantation created hope for a cure of diabetes,” says Karin Katz, MD and Loren Wissner Greene, MD, MA., in an article for Clinical Correlations. “However, in many cases the ‘Edmonton procedure’ has failed to live up to its expectations. Multiple donors are needed for each islet cell infusion, and patients require repeated transplants to achieve insulin independence. An international trial of islet cell transplants found that 66% of the recipients required conventional insulin therapy within a year and 75% after 2 years. Recipients also need to be maintained on lifelong immunosuppression, which is associated with a myriad of complications.”

That would seem like the end of the story, but more than a decade later, islet cell transplantation is still progressing.

The first reason is because of research being conducted in Australia, at Sydney’s Westmead Institute for Medical Research.

“There’s has always been some talk that the liver might not be most beneficial place to implant islet cells,” says Rebecca Stokes, lead researcher into a study to explore other locations for implanting islet cells. “The liver is a large organ and you get a lot of blood flow, which is thought to be good for circulating insulin. But, you also get a lot immune cells coming in and that makes the new cells very susceptible to immune attack.”

Additionally, while the implantation procedure itself is minor—it’s just putting a large needle into the portal vein and pressing the plunger until the cells are infused—it carries potential complications such as bleeding and blood clots. So, if the procedure can be avoided, it would be beneficial.

Stokes’s team compared implanting mouse and human islet cells, into both mice and pigs, into the liver, kidney, spleen, and quadriceps muscles. It turns out that infusing the islet cells into the quadriceps muscles worked just as well, if not better than infusing them into the portal vein leading to the liver, Stokes says.

“It’s a hope to study this in people,” she adds.

Stokes says that researchers at Westmead are also working to solve another problem that hangs over islet cell transplantation: the availability of the islet cells themselves.

Like any whole organ transplant, each infusion of islet cells requires cells donated from the pancreases of people who have recently died. Unlike, say a heart or liver transplant, each infusion of islet cells often requires multiple donors and multiple infusions, further limiting the supply of cells.

“We’re also working on xenotransplantation,” Stokes says of the process of transplanting islet cells from pigs into humans. “Pigs to primate studies have shown promise, along with the genetic modification of porcine cells.”

But, if islet cell transplantation is not considered an effective cure for diabetes, why bother improving the effectiveness of how it can be done? Because it turns out that while it’s not a cure, researchers in Korea have determined that the procedure does offer some therapeutic benefits.

“Although initially expected to therapeutically target long-term insulin independence, islet transplantation is now indicated for more specific clinical benefits,” say researchers Sang-Man Jim and Kwang-Won Kim in research published by the United States National Institutes of Health in January 2017.

Specifically, the paper says islet cell transplantation is a treatment for chronic pancreatitis, is effective at preventing diabetes after partial pancreatectomy for benign pancreatic tumors, and, more broadly, is also effective in treating subjects with severe hypoglycemia.

While it’s not understood why this benefit occurred, in some ways that’s missing the point. When it comes to research, when it comes to moving forward to find out answers so people might benefit, this seems like a case where it’s better to try and find out than be satisfied not knowing. Insulin therapy keeps us going, but it’s not enough.

 

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