A study led by researchers at Weill Cornell Medicine has demonstrated that engineered human blood vessel-forming cells can significantly improve the survival of insulin-producing islet cells, effectively reversing diabetes in a preclinical model. This promising approach, published in Science Advances, could pave the way for more effective islet transplantation strategies to treat type 1 diabetes.
Islets, located within the pancreas, contain insulin-producing cells that regulate blood sugar levels. In type 1 diabetes, an autoimmune reaction destroys these cells, leading to lifelong dependence on insulin therapy. Although islet transplantation has shown potential as a treatment, the current FDA-approved method has substantial limitations. The procedure involves injecting islets into a liver vein, which requires long-term immunosuppression and often results in islet failure within a few years due to a lack of proper support cells.
Seeking a more viable alternative, the research team developed “reprogrammed vascular endothelial cells” (R-VECs) to serve as support structures for transplanted islets. These engineered cells enhance islet survival by forming robust blood vessel networks, ensuring an adequate supply of oxygen and nutrients. The study demonstrated that R-VECs enabled the successful long-term engraftment of human islets when transplanted under the skin of mice, an approach that could provide a safer and more durable treatment option for diabetes patients.
According to the researchers, this work lays the foundation for subcutaneous islet transplants as a relatively safe and durable treatment option for type 1 diabetes. Unlike natural islet endothelial cells, which are fragile and prone to degradation in transplant conditions, R-VECs are derived from human umbilical vein cells and are highly adaptable. They support the formation of new blood vessels and even adopt the genetic characteristics of native islet endothelial cells, effectively integrating into the surrounding tissue. Vascularized human islets implanted into the subcutaneous tissue of immune-deficient mice promptly connected to the host circulation, providing immediate nutrition and oxygen, thereby enhancing the survival and function of the vulnerable islets.
The results were striking as most diabetic mice that received islets in combination with R-VECs regained normal body weight and maintained stable glucose levels for over 20 weeks, suggesting that the transplanted islets remained functional indefinitely. In contrast, mice that received islets without R-VECs experienced significantly lower success rates.
The researchers successfully cultivated islet-R-VEC combinations in microfluidic devices, which could be instrumental in testing new diabetes treatments. They also emphasized the need for further testing and stated that the potential of surgical implantation of these vascularized islets needs to be examined for their safety and efficiency in large animal models. Despite the promising findings, several challenges remain before this method can be widely applied to human patients. Scaling up the production of vascularized islets and developing immune-evasion strategies to eliminate the need for immunosuppressive drugs are critical hurdles to overcome.
This study is the first step in achieving these goals, which could be within reach in the next several years. If successfully translated to clinical practice, this innovative technique could revolutionize the treatment of type 1 diabetes, offering patients a safer, more effective alternative to conventional insulin therapy.
Reference
- Li G, Craig-Schapiro R, Redmond D, Chen K, Lin Y, Geng F, et al. Vascularization of human islets by adaptable endothelium for durable and functional subcutaneous engraftment. Sci Adv. 2025 Jan 31;11(5):eadq5302.