Getting under the skin: UAlberta research reveals new possibilities for islet and stem cell transplantation

Research opens new treatment avenues for regenerative medicine.

Ross Neitz - 21 April 2015

James Shapiro, one of the world's leading experts in emerging treatments of diabetes, can't help but be excited about his latest research. The results, he says, could soon mark a new standard for treatment-not only in diabetes, but in several other diseases as well.

Shapiro, Canada Research Chair in Transplantation Surgery and Regenerative Medicine in the University of Alberta's Faculty of Medicine & Dentistry, along with Andrew Pepper, a post-doctoral fellow working in his lab, are the lead authors in a study published in the April 20 edition of the journal Nature Biotechnology. In the study, the authors describe developing a new site for islet transplantation under the skin, which they believe will offer less risk and far greater health benefits for patients.

Islet transplantation is a procedure that temporarily allows severe diabetics to stop taking insulin.

"Until now it has been nearly impossible for transplanted cells to function reliably when placed beneath the skin," says Shapiro. "In these studies, we have harnessed the body's natural ability to respond to a foreign body by growing new enriching blood vessels. By controlling this reaction, we have successfully and reliably reversed diabetes in our preclinical models. This approach is new and especially exciting as it opens up a new world of opportunities, not only in diabetes, but also across the board in regenerative medicine."

The new technique, tested in preclinical models, is an evolution of the Edmonton Protocol, which Shapiro developed in the late 1990s to treat Type 1 diabetes. In the Edmonton Protocol, islet cells are transplanted into the liver, granting patients insulin independence for a varying amount of time. While hailed as a revolutionary treatment, Shapiro quickly realized the liver wasn't the ideal site for transplantation.

"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," says Shapiro. "As we turn to the future possibility of transplanting human stem cells in place of islets, we need a better, safer site to implant experimental cells. The skin offers a remarkable opportunity, provided we can enrich its blood supply to accommodate the needs of implanted cells."

As Shapiro's team began testing alternatives, sites underneath the skin first proved inhospitable for the cells due to a lack of blood vessels needed for the islets to grow and reproduce. As part of their research though, they found that by inserting a temporary catheter tube under the skin, new blood vessels could be induced to grow, making an ideal home for islet transplantation.

"In the paper, what we show is that when we put the cells under the skin on their own, they fail every single time," says Shapiro. "They never engraft. If we put the cells into a site that's been prepared by what we call our 'deviceless' approach, then we can get the cells to engraft highly efficiently."

"This is a promising new procedure of transplanting cells into a site with the body that until now has historically failed," says Pepper. "We have clearly demonstrated that our novel technique has the potential to be applied safety and easily to patients."

While the new transplant approach offers several benefits to diabetes patients, the researchers are equally excited by how it may be applied to other illnesses as well. Shapiro says his team is also testing its use in stem cell transplantations, which, if successful, could safely open the door to allow for the assessment of emerging stem cell treatments.

"It opens up the possibility of being able to transplant stem cells into patients in a site that can be removed," says Shapiro. "That's been a big focus when you've got a new cell line that's never been tested in patients before. The ability to take the cells out if there's a problem is very important."

Shapiro adds, "This exciting new approach doesn't have to be limited to diabetes. 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."

Shapiro has filed a patent for the new transplant technique and hopes to begin human trials in the very near future.

Research funding was provided by the Diabetes Research Institute Foundation of Canada, Collaborative Research & Innovation Opportunities, Alberta Innovates:Health Solutions and the University Hospital Foundation.