Objective
The objective of this research is to produce high-quality islets from human pluripotent stem cells and combine them with biomaterials to improve survival after transplantation for use in cell replacement therapy. We will study the function, composition, and identity of the produced islets with the biomaterial to ensure they survive and function in a manner compatible with Type 1 diabetes cell replacement therapy.
Background Rationale
Type 1 diabetes results from the destruction of insulin-producing pancreatic islets. Transplantation of exogenous islets could potentially cure patients. However, the supply of donor cells is very limited and of varying quality, rendering this approach impractical for the millions of patients who could benefit. We have developed methods for making functional islets from human pluripotent stem cells in vitro. These stem cell-derived islets (SC-islets) have many of the features of adult islets and can alleviate diabetes in mouse models. SC-islets are a renewable, virtually limitless cell source that overcomes current shortages of donor cells. However, currently, most cells die shortly after transplantation for the treatment of Type 1 diabetes. We hypothesize that combination with specialized biomaterials can improve the survival of SC-islets to maximize their functional efficacy in patients.
Description of Project
The escalating prevalence of Type 1 diabetes has ignited a significant focus on advancing technologies for a more thorough understanding and enhanced treatment of this condition. Given the absence of a definitive cure for Type 1 diabetes, existing diabetic therapies often fall short in effectively managing the disease for numerous patients. An innovative avenue for potential cure lies in the transplantation of exogenous islets. In our research, we have pioneered methodologies to generate an essentially limitless supply of functional islets from human pluripotent stem cells within the laboratory setting. Our current proposal seeks to elevate this manufacturing process to new heights by refining its intricacies. Additionally, we aim to investigate the integration of biomaterials into the process to augment the post-transplantation survival rates. This dual-pronged approach not only holds promise for revolutionizing the treatment landscape for Type 1 diabetes but also underscores our commitment to pushing the boundaries of scientific innovation in the pursuit of a viable cure.
Anticipated Outcome
The expected outcome of this contribution is a detailed methodology for generating high-quality islets from stem cells. The outcome of this proposal will have a positive impact by supplying these cells to the field and providing a biomaterial strategy for keeping them alive after transplantation. Successful completion of our studies will provide an improved and complete strategy for stem cell-derived islets for use in diabetes cell replacement therapy.
Relevance to T1D
This proposal is highly relevant to Type 1 diabetes and aims to increase our knowledge of how to effectively transplant stem cell-derived islets into patients for better survival rates. This would ultimately improve the chances of the recipient no longer needing insulin injections. The use of stem cells with our differentiation approach provides a potentially unlimited number of stem cell-derived insulin-producing islets for applications that are very important to Type 1 diabetic patients. The cellular products we generate could be transplanted into Type 1 diabetic patients, with these exogenous cells replacing the function lost in the endogenous islets, thus controlling patient blood glucose without insulin injections.