They Offer a New Approach to Islet Transplants for Type 1 Diabetes

American researchers have discovered a mechanism to increase the long-term viability of pancreatic islet transplants by using reprogrammed vascular endothelial cells for support.

The pancreatic islet is the only type of tissue in humans that secretes insulin in response to elevated glucose levels and plays a crucial role in the prevention and treatment of all types of diabetes. Native pancreatic islets are scattered throughout the pancreas, contributing approximately 2% of the pancreatic mass but receiving up to 20% of the pancreas's blood supply due to the islets' extensive vascularization.

In a recent study published in Science Advances, researchers from Weill Cornell Medicine in New York (USA) demonstrated that special blood vessel-forming cells, known as “reprogrammed vascular endothelial cells” (R-VEC), can provide strong support to islets, enabling them to survive and reverse diabetes long-term when transplanted under the skin, in this case, of mice.

“This work lays the groundwork for subcutaneous islet transplants as a relatively safe and durable treatment option for type 1 diabetes,” explained the lead author, Ge Li, postdoctoral research associate in the lab of the principal investigator, Dr. Shahin Rafii, who is also the director of the Hartman Institute for Therapeutic Regeneration of Organs and the Ansary Stem Cell Institute.

Currently, the approved islet transplant method involves infusing islets into a vein in the liver. This invasive procedure requires long-term use of immunosuppressive drugs to prevent islet rejection, involves relatively uncontrolled dispersion of the islets, and often becomes ineffective after a few years, likely due in part to a lack of appropriate support cells, according to the authors.

Implant in a More Controlled and Accessible Area

Ideally, the researchers believe they could find a method to implant islets in a more controlled and accessible location, such as under the skin, where the transplanted tissue could survive indefinitely. They also hope to eventually overcome 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, these scientists demonstrated the long-term viability of subcutaneous islet transplants using R-VEC as critical support cells. "We found that human vascularized islets implanted in the subcutaneous tissue of immunodeficient mice quickly connected to the host’s circulation, providing immediate nutrition and oxygen, thereby improving the survival and function of vulnerable islets," explained Prof. Rafii.

The authors observed that R-VEC adapted when co-transplanted with islets, supporting the islets with a rich network of new blood vessels and even assuming the genetic activity signature of natural islet endothelial cells.

Furthermore, the team showed that combinations of islet cells and R-VEC could successfully grow in small “microfluidic” devices, which could be used for rapid testing of potential diabetes medications.

“Ultimately, the surgical implantation potential of these vascularized islets needs to be examined to determine their safety and effectiveness in large animal models,” stated co-author Dr. Rebecca Craig-Schapiro, assistant professor of surgery at Weill Cornell Medicine and transplant surgeon at NewYork-Presbyterian/Weill Cornell Medical Center.

https://www.immedicohospitalario.es/noticia/49970/aportan-un-nuevo-enfoque-en-los-trasplantes-de-islotespara-la-diabet.html