Transplanting islet cells along with blood vessel cells can effectively treat type 1 diabetes.

A new approach, which requires further development and testing, may allow for a much broader use of islet transplantation in the treatment of diabetes in the future.

The islet, located in the pancreas, is a cluster of insulin-secreting and other cells surrounded by tiny specialized blood vessels. In cases of type 1 diabetes, which affects about nine million people worldwide, insulin-producing cells die due to an autoimmune process. Although islet transplantation is a promising method for treating these cases, the only FDA-approved technique to date has significant limitations.

In a study published in Science Advances, researchers demonstrated that their specially developed blood vessel-forming cells, known as "reprogrammed vascular endothelial cells" (R-VEC), can overcome some of these limitations by providing reliable support to the islets, allowing them to survive and effectively manage diabetes when transplanted under the skin of mice.

"This work lays the groundwork for subcutaneous islet transplantation as a relatively safe and long-term treatment method for type 1 diabetes," says the lead author of the study, Dr. Ge Li, a postdoctoral researcher in Dr. Shahin Rafii's laboratory.

According to the currently approved method of islet transplantation, they are introduced into a vein in the liver. This invasive procedure requires long-term use of immunosuppressive drugs to prevent rejection of the islets, involves relatively uncontrolled dispersion of the islets, and typically loses effectiveness within a few years, likely due in part to the lack of proper supportive cells.

Ideally, researchers seek a method that allows islets to be implanted in a more controlled and accessible location, such as under the skin, and enables the transplanted tissue to survive indefinitely. Researchers also hope to eventually bypass the issue of immune rejection by using islets and endothelial cells derived from the patients' own cells or designed to be invisible to the immune system.

In the new study, scientists demonstrated the feasibility of long-term subcutaneous islet transplantation using R-VEC as crucial supportive cells. "We showed that vascularized human islets, implanted into the subcutaneous tissue of immunocompromised mice, quickly connect to the host's circulation, providing immediate nourishment and oxygen, thereby increasing the survival and functionality of vulnerable islets," says Dr. Rafii.

Indeed, derived from human umbilical vein cells, R-VEC are relatively durable in transplantation—unlike the fragile endothelial cells found in islets—and are designed to adapt well, supporting any specific type of surrounding tissue.

Notably, when co-transplanted with islets, researchers found that R-VEC do indeed adapt, supporting the islets with a rich network of new blood vessels and even acquiring the "signature" gene activity of natural islet endothelial cells.

A significant majority of diabetic mice that received islets plus R-VEC regained normal body weight and exhibited normal blood glucose control even after 20 weeks—a timeframe that for this mouse model of diabetes indicates effective long-term engraftment of the islets. Mice that received islets but not R-VEC fared much worse.

In their study, the team showed that the combination of islet cells and R-VEC can also successfully grow in small "microfluidic" devices that can be used for rapid testing of potential diabetes drugs.

Ultimately, the potential for surgical implantation of these vascularized islets needs to be investigated for safety and efficacy in larger animal models.