Engineered human blood vessel-forming cells added to islet transplants have proven successful in enhancing insulin-producing cell survival and reversing diabetes in preclinical research led by investigators from Weill Cornell Medicine. This innovative approach, though still requiring further development and testing, holds potential for significantly expanding the use of islet transplants as a treatment option for diabetes.
Islets are clusters found within the pancreas containing insulin-secreting cells enmeshed in specialized blood vessels. In type 1 diabetes, which affects approximately nine million people worldwide, these insulin-producing cells are destroyed by an autoimmune response. While islet transplantation shows promise as a treatment method for this condition, it has significant limitations under current FDA-approved procedures.
In a study published on January 29 in Science Advances, researchers demonstrated the effectiveness of special blood vessel-forming cells they developed called “reprogrammed vascular endothelial cells” (R-VECs). These R-VECs provide substantial support for islets when transplanted under mouse skin, allowing them to survive and reverse diabetes over a long period.
“This work establishes the groundwork for subcutaneous islet transplants as a potentially safe and enduring treatment method for type 1 diabetes,” stated Dr. Ge Li, the first author of this study and a postdoctoral research associate in senior author Dr. Shahin Rafii’s laboratory. Dr. Rafii holds positions including director of the Hartman Institute for Therapeutic Organ Regeneration and the Ansary Stem Cell Institute, chief of regenerative medicine at Weill Cornell Medicine, Arthur Belfer Professor in Genetic Medicine, member of the Englander Institute for Precision Medicine and Sandra and Edward Meyer Cancer Center.
The current FDA-approved islet transplantation method involves infusing them into a liver vein through an invasive procedure. This approach necessitates long-term use of immune-suppressing drugs to prevent rejection and typically becomes ineffective within a few years, partly due to the lack of supportive cells around the transplanted tissue. Ideal treatment would involve placing islets in a controlled location like under the skin, allowing them to thrive indefinitely without immune rejection.
In their study, Drs. Li and Rafii demonstrated that long-term subcutaneous transplantation using R-VECs as support cells is feasible. “We showed that vascularized human islets implanted into mice with suppressed immunity quickly connected to the host circulation, supplying immediate nutrition and oxygen, which significantly enhanced both the survival and function of these vulnerable cells,” explained Dr. Rafii.
Derived from human umbilical vein cells, R-VECs are more durable in transplant conditions than fragile endothelial cells found naturally within islets and can adapt to various surrounding tissues when transplanted together with islets. The results showed that not only did R-VECs support the growth of new vessels around the islets but also took on gene activity signatures typical of natural islet endothelial cells.
Over 20 weeks, a significant majority of diabetic mice received both islet transplants and R-VECs regained normal body weight and achieved stable blood glucose levels. In contrast, those receiving only islets had much poorer outcomes. The team also demonstrated that these vascularized islet-cell combinations could grow successfully in small “microfluidic” devices used for testing potential diabetes medications.
“The next step involves further preclinical studies to examine the safety and efficiency of surgically implanting these vascularized islets,” said Dr. Rebecca Craig-Schapiro, a co-author and assistant professor of surgery at Weill Cornell Medicine as well as a transplant surgeon at NewYork-Presbyterian/Weill Cornell Medical Center. “Despite this progress, transitioning this technology to treat patients with type 1 diabetes will require overcoming several challenges including producing enough vascularized islets and devising ways to avoid immunosuppression.”
Though still in early stages, Dr. Li noted that achieving these goals could be possible within the next few years.
