In a groundbreaking study, researchers have discovered that adding engineered human blood vessel-forming cells to islet transplants significantly enhances the survival of insulin-producing cells and reverses diabetes in preclinical models. This innovative approach, published on Jan. 29 in Science Advances, holds promise for the broader application of islet transplants as a cure for diabetes.

Islets, found in the pancreas, are clusters of insulin-secreting and other cells enmeshed in tiny, specialized blood vessels. In type 1 diabetes, an autoimmune process destroys these insulin cells, affecting roughly nine million people worldwide. Although islet transplantation is a promising treatment, the only FDA-approved method has significant limitations.

The study introduced “reprogrammed vascular endothelial cells” (R-VECs), engineered to provide strong support for islets, allowing them to survive and reverse diabetes long-term when transplanted under the skin of mice. “This work lays the foundation for subcutaneous islet transplants as a relatively safe and durable treatment option for type 1 diabetes,” said Dr. Shahin Rafii, director of the Hartman Institute for Therapeutic Organ Regeneration and the Ansary Stem Cell Institute at Weill Cornell Medicine.

The currently approved islet-transplant method infuses islets into a vein in the liver, an invasive procedure requiring long-term immune-suppressing drugs to prevent rejection. This method often becomes ineffective within a few years due to the lack of proper support cells. Researchers aim for a more controlled and accessible site, such as under the skin, and hope to eventually sidestep immune rejection by using islets and endothelial cells derived from patients’ own cells or engineered to be invisible to the immune system.

In the new study, researchers demonstrated the feasibility of long-term subcutaneous islet transplants using R-VECs as critical support cells. “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,” said Dr. Rafii. Derived from human umbilical vein cells, R-VECs are relatively durable in transplant conditions and are engineered to be highly adaptable, supporting whatever specific tissue type surrounds them.

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, said Dr. David Redmond, an assistant professor of computational biology research in medicine in the Hartman Institute for Therapeutic Organ Regeneration.

A substantial 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 suggesting an effectively permanent islet engraftment. Mice that received islets but no R-VECs fared much less well.

The team also showed that the islet cell and R-VEC combinations can grow successfully in small “microfluidic” devices, which can be used for the rapid testing of potential diabetes drugs. “Ultimately, the potential of surgical implantation of these vascularized islets needs to be examined for their safety and efficiency in large animal models,” said Dr. Rebecca Craig-Schapiro, an assistant professor of surgery at Weill Cornell Medicine and a transplant surgeon at NewYork-Presbyterian/Weill Cornell Medical Center.

Nonetheless, 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, said Dr. Li. This study is the first step to achieve these goals, which could be within reach in the next several years.

While the study is promising, it is essential to address potential counterarguments. Critics may point out that the long-term efficacy and safety of R-VECs in human trials remain uncertain. Additionally, the scalability of producing sufficient R-VECs for widespread use is a significant challenge. However, the study’s findings provide a robust foundation for further research and development in this area.

Recent developments in regenerative medicine and stem cell research have brought us closer to realizing the potential of islet transplants. For instance, advancements in tissue engineering and 3D bioprinting could enhance the production and implantation of vascularized islets. Moreover, ongoing research into immune tolerance and personalized medicine may pave the way for more effective and less invasive treatments for type 1 diabetes.

In conclusion, the study’s findings represent a significant milestone in the quest for a cure for type 1 diabetes. By leveraging engineered blood vessel-forming cells, researchers have demonstrated a novel approach to enhancing islet survival and function. As the technology advances, it holds the potential to transform the lives of millions of Americans living with diabetes.