Revolutionary Blood Vessel Cells Enhance Success of Islet Transplants for Diabetes Treatment

In a groundbreaking preclinical study conducted by investigators from Weill Cornell Medicine, incorporating engineered human blood vessel-forming cells into islet transplants significantly enhanced the survival of insulin-producing cells and reversed diabetes. This novel approach, though still under development and testing, holds promise for expanding the use of islet transplants as an effective cure for diabetes.

Islets are clusters of insulin-secreting and other cell types found within the pancreas, embedded in tiny specialized blood vessels. In type 1 diabetes, these insulin cells are destroyed by autoimmune processes that affect approximately nine million people globally. While islet transplantation offers a promising treatment option for this condition, the only FDA-approved method has notable limitations.

A study published on January 29th in Science Advances showcased how special blood vessel-forming cells created by the researchers—referred to as “reprogrammed vascular endothelial cells” (R-VECs)—could address these shortcomings. By providing robust support for islets, R-VECs enabled them to survive and reverse diabetes in mice when transplanted beneath their skin.

“This research establishes a foundation for subcutaneous islet transplantation as a relatively safe and durable treatment option for type 1 diabetes,” noted Dr. Ge Li, the study’s first author and a postdoctoral researcher in Dr. Shahin Rafii’s lab at Weill Cornell Medicine. “Dr. Rafii also leads the Hartman Institute for Therapeutic Organ Regeneration, the Ansary Stem Cell Institute, and is an esteemed member of several other prestigious research centers within Weill Cornell Medicine,” including the Englanger Institute for Precision Medicine and the Sandra and Edward Meyer Cancer Center.

The current FDA-approved method involves infusing islets directly into a liver vein. This procedure demands lifelong use of immunosuppressive drugs to prevent rejection, often results in unpredictable dispersal of islets, and typically becomes ineffective within several years due to inadequate support cells.

Researchers aspire to develop a more controlled method for transplanting islets, ideally under the skin where they could indefinitely survive. Eventually, efforts aim to eliminate immune rejection by using patient-derived or engineered cells invisible to the immune system.

In their new study, Drs. Li and Rafii and their team demonstrated the viability of long-term subcutaneous islet transplants with R-VECs as critical support cells. “We found that vascularized human islets implanted into immunodeficient mice immediately connected to host circulation, receiving essential nutrition and oxygen, which significantly improved both survival and function of these vulnerable islets,” Dr. Rafii explained.

R-VECs, derived from human umbilical vein cells, are notably durable under transplant conditions compared to fragile endothelial cells found in islets. These engineered cells also exhibit high adaptability, supporting the surrounding tissue type effectively.

Interestingly, when co-transplanted with islets, R-VECs adapted by forming a rich network of new vessels and acquiring gene activity signatures resembling natural islet endothelial cells. In substantial majority of diabetic mice receiving transplants of islets along with R-VECs, body weight normalized and blood glucose levels returned to normal even after 20 weeks—a duration that suggests permanent engraftment in this mouse model.

Furthermore, the team demonstrated successful growth of islet-RVEC combinations within small “microfluidic” devices, which can be used for rapid testing of potential diabetes medications. However, Dr. Rebecca Craig-Schapiro, an assistant professor of surgery at Weill Cornell Medicine and a transplant surgeon at NewYork-Presbyterian/Weill Cornell Medical Center highlighted that further preclinical safety and efficiency studies are necessary before surgical implantation.

“While overcoming significant hurdles remains crucial—such as scaling up vascularized islets and devising methods to avoid immunosuppression—the translation of this technology for treating type 1 diabetes could be within reach in the next few years,” Dr. Li concluded, underscoring the potential impact of their pioneering research.