Objective
The objective of this research is to improve stem cell-derived islets by embedding them with their own blood vessels, similar to natural pancreatic islets. Our goal is to determine whether adding these built-in blood vessels improves the survival and function of the islets after they are transplanted into diabetic recipients. This work will support the development of more effective cell-based therapies for Type 1 diabetes.
Background Rationale
Type 1 diabetes is caused by the immune system destroying the insulin-producing cells in the pancreas. One way to potentially cure this disease is by replacing those lost cells through islet transplantation. However, donor islets are scarce and often of inconsistent quality, limiting the number of patients who can benefit. To overcome this, we have developed methods to create insulin-producing islets from human stem cells in the lab. These stem cell-derived islets (SC-islets) show promise in animal models, but they are still not fully mature and tend to die soon after transplantation. We believe this is because they lack the small blood vessels that are normally found inside real islets and are essential for delivering oxygen and nutrients. In this project, we aim to add those missing blood vessels into SC-islets to improve their survival and ability to control blood sugar after transplantation.
Description of Project
Type 1 diabetes remains an incurable disease that requires lifelong insulin therapy and often leads to serious complications. Transplanting insulin-producing islets offers the potential for a lasting cure, but donor islets are scarce, and survival after transplantation is poor. We have developed a method to generate unlimited numbers of islets from human stem cells in the lab. In this project, we propose to improve these lab-grown islets by engineering them with a built-in vascular system, similar to natural islets. We believe that by embedding blood vessels within the islets, we can improve their survival, integration, and ability to control blood sugar after transplantation, bringing us closer to a curative therapy for Type 1 diabetes.
Anticipated Outcome
The expected outcome of this research is a clearer understanding of how adding blood vessels inside stem cell-derived islets influences their survival and function after transplantation. We aim to show whether this built-in vasculature helps the islets live longer and work better in controlling blood sugar. This knowledge will guide future improvements in how SC-islets are designed for use in treating Type 1 diabetes and could help make cell replacement therapy more effective and reliable.
Relevance to T1D
This proposal is highly relevant to Type 1 diabetes because it addresses a major barrier in the development of effective cell therapies—poor survival of transplanted islets. By engineering stem cell-derived islets with their own blood vessels, we aim to increase their ability to survive and function in the body, reducing or eliminating the need for insulin injections. Our approach uses human stem cells to generate a renewable supply of insulin-producing islets, making this strategy scalable and potentially available to many patients. If successful, these vascularized SC-islets could be transplanted into individuals with Type 1 diabetes to restore natural blood sugar control and reduce dependence on insulin therapy.