Engineered Cells Revolutionize Islet Transplants, Offering hope for Type 1 Diabetes Cure

A major breakthrough in type 1 diabetes treatment has emerged from a preclinical study by Weill Cornell Medicine researchers. Published Jan. 29 in Science Advances, the study shows that adding engineered human blood vessel-forming cells to islet transplants dramatically improves the survival rate of insulin-producing cells and reverses diabetes in mice. This innovative approach could revolutionize treatment for the roughly 9 million people worldwide affected by type 1 diabetes.

Islet transplantation, while promising, currently faces significant limitations. The only FDA-approved method involves infusing islets into a liver vein, requiring long-term immunosuppressant drugs to prevent rejection. This method also leads to uncontrolled islet dispersal and typically loses effectiveness within a few years, partly due to a lack of adequate support cells. “The currently approved islet-transplant method infuses islets into a vein in the liver. This invasive procedure requires the long-term use of immune-suppressing drugs to prevent islet rejection, involves the relatively uncontrolled dispersal of islets, and usually becomes ineffective within a few years, likely in part to the lack of proper support cells,” explains the study.

The Weill Cornell Medicine team, led by Dr. shahin Rafii, director of the Hartman Institute for Therapeutic Organ Regeneration and the Ansary Stem Cell Institute, developed “reprogrammed vascular endothelial cells” (R-VECs).These cells, derived from human umbilical vein cells, are remarkably durable and adaptable, providing crucial support for transplanted islets. dr. Rafii, also chief of the division of regenerative medicine and the Arthur B. Belfer Professor in Genetic Medicine at Weill Cornell Medicine, highlighted the findings’ significance: “This work lays the foundation for subcutaneous islet transplants as a relatively safe and durable treatment option for Type 1 diabetes,” he said. He further elaborated, “We showed that vascularized human islets implanted into the subcutaneous tissue of mice that were immune-deficient promptly connected to the host circulation, providing immediate nutrition and oxygen, thereby enhancing the survival and function of the vulnerable islets.”

The study’s first author, Ge Li, a postdoctoral research associate in Dr. Rafii’s laboratory, and colleagues demonstrated the efficacy of this approach. Thay co-transplanted islets with R-VECs under the skin of immune-deficient mice. The results were striking. “A majority of diabetic mice transplanted with islets-plus-R-VECs regained normal body weight and showed normal blood glucose control even after 20 weeks – a period that for this mouse model of diabetes suggests an effectively permanent islet engraftment. Mice that received islets but no R-VECs fared much less well,” the study reported. This long-term success suggests a potential for a permanent solution to type 1 diabetes.

Dr. David Redmond, an assistant professor of computational biology research in medicine in the Hartman institute for Therapeutic Organ Regeneration, highlighted the adaptability of the R-VECs: “Remarkably, we found that R-VECs did adapt when co-transplanted with islets, supporting the islets with a rich mesh of new vessels and even taking on the gene activity ‘signature’ of natural islet endothelial cells,” he noted. This adaptation ensures the R-VECs effectively integrate with the transplanted islets, creating a robust and enduring habitat.

The researchers also demonstrated the potential for using these vascularized islets in small microfluidic devices for rapid drug testing. 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, cautioned that further research is needed: “Ultimately, the potential of surgical implantation of these vascularized islets needs to be examined for their safety and efficiency in large animal models,” she stated.

While this research represents a significant advancement, Ge Li acknowledged the challenges ahead: “Translation of this technology to treat patients with type 1 diabetes will require circumventing numerous hurdles, including scaling up sufficient numbers of vascularized islets, and devising approaches to avoid immunosuppression,” Li said. This study, however, provides a crucial first step towards a potential cure for type 1 diabetes.

Dr. Rafii is an unpaid co-founder of Angiocrine Bioscience.This work was supported by grants from the National Institutes of Health, the Juvenile Diabetes Research Foundation, and the Hartman Institute for Therapeutic Organ Regeneration, the Ansary Stem Cell Institute, the Division of Regenerative Medicine, and the selma and lawrence Ruben Daedalus Fund for Innovation at Weill Cornell Medicine.