Objective
The goal of this research program is to design an immune intervention utilizing thymic cotransplants within the lymph node that will preserve pancreatic islet graft function without exposing patients to the risks of chronic systemic immunosuppression.
Background Rationale
Type 1 diabetes (T1D) occurs when the body’s immune system mistakenly attacks and destroys the cells in the pancreas that make insulin. Without insulin, the body cannot properly regulate blood sugar, and patients must rely on insulin injections for life. Although insulin treatment prevents immediate crises, it cannot perfectly control blood sugar or prevent long-term complications affecting the eyes, kidneys, nerves, and heart.
Transplanting insulin-producing islets from a donor pancreas is a promising treatment for people with difficult-to-control T1D, especially those who experience dangerous low blood sugars. The goal is to replace the missing cells so the body can produce its own insulin again. A breakthrough in 2000 (the Edmonton protocol) showed that islet transplantation could restore insulin production without using steroids, allowing many patients to stop taking insulin entirely. Over time, many transplants lose their ability to make insulin, and the medications needed to protect the transplanted cells can cause serious side effects such as infections or kidney damage. The immune system poses two major challenges: it may repeat the same autoimmune attack that caused diabetes, and it may reject the donor’s cells as foreign. To prevent this, patients must take powerful immune-suppressing drugs for life.
Demonstrating a Cure Is Possible: Islet transplantation proves that replacing insulin-producing cells can reverse diabetes. Even partial recovery helps patients avoid dangerous low blood sugars and achieve more stable control. Exciting new research using stem cells shows that lab-grown β-cells can function like natural ones, potentially providing an unlimited source for future transplants. The main obstacle is that patients must take drugs to prevent rejection, which can cause infections and other health risks. To make islet transplants widely available, we need better ways to protect the new cells—methods that are both effective and safe for long-term use. Scientists are developing ways to protect transplanted cells without toxic drugs. Strategies include using “peacekeeping” immune cells that prevent attack, shielding islets in protective capsules, or teaching the immune system to accept new cells as its own. If these work, islet transplantation could become a safe and lasting cure for diabetes. Despite major advances, few patients can benefit today because of the side effects of current drugs. Solving this problem will not only make islet transplants safer but also pave the way for new regenerative treatments using stem cell–derived insulin-producing cells for everyone with Type 1 diabetes.
Islet transplantation shows that curing Type 1 diabetes is possible. The next step is to protect these new cells safely—without lifelong immune suppression. Achieving this would make cell therapy practical, safe, and transformative for millions of people living with diabetes.
Description of Project
This proposed research is committed to advancing the development of islets transplantation that can restore blood sugar control and eliminate the need for exogenous insulin administration in people with Type 1 Diabetes. It is based on published and successful preclinical proof of concept data showing lymph nodes have characteristics that make them useful sites for transplantation. Transplantation of pancreatic islets into lymph node has demonstrated therapeutic effects in diabetic mice, and it represents a potential novel therapeutic site for diabetic patients. Furthermore, transplantation of cells or tissues into lymph nodes can be done via endoscopic ultrasound, an outpatient procedure currently used to transplant primary human cells in clinical trial. Pancreatic islets could similarly be transplanted to lymph node via endoscopic ultrasound. Finally, lymph node can be used to train the immune system to not react destructively to reject islets. In conclusion, this proposal study advances our use of the lymph node as an in vivo bioreactor to exert remarkable therapeutic outcomes for pancreatic islets and has important potential clinical application for Type 1 Diabetes.
Anticipated Outcome
Pancreatic islet transplantation offers a compelling proof-of-principle that β-cell replacement can reverse T1D, but its success is inseparably tied to immunosuppression. The major challenge now is to design immune interventions that preserve graft function without exposing patients to the risks of chronic systemic immunosuppression. We are proposing to achieve this goal which will not only expand access to islet transplantation but also accelerate the development of safe and effective cell replacement therapies for T1D.
Relevance to T1D
This proposed research is committed to advancing the development of allogeneic islets transplantation that can restore glycemic control and eliminate the need for exogenous insulin administration in people with T1D. It is based on published and successful preclinical proof of concept data showing lymph nodes have characteristics that make them useful sites for transplantation islets for Type 1 Diabetes.