Objective
The objective of this project is to improve treatments for Type 1 diabetes (T1D) by developing better cell therapies. In T1D, the body’s immune system destroys the insulin-producing beta cells in the pancreas, leading to poor control of blood sugar levels. Our project focuses on creating and testing new cell-based therapies using stem cells that are turned into insulin-producing beta cells and glucagon-producing alpha cells. We aim to understand how the right balance and arrangement of these cells in a transplant can restore normal blood sugar control. By studying how these cells interact and communicate with each other, we hope to develop a therapy that more closely mimics the natural function of the pancreas, providing a potential cure for T1D.
Background Rationale
The development of cell replacement therapies for T1D has been a major focus of research and development. The development of differentiation protocols to direct pluripotent stem cells toward pancreatic cell types are now common, although these differentiation protocols produce a heterogenous cell population. Most of these protocols have been developed with the primary goal of producing SC-beta cells, although all protocols contain off-target cell types. While protocols have matured to produce more functionally mature beta cells, the nature, proportion and function of the side population cells remains uncontrolled. Nonetheless, these cell products have demonstrated significant therapeutic promise and are now showing encouraging results in clinical studies.
Despite these advances several significant questions remain. Does the proportion of alpha and beta cells produced in current differentiation protocols adequately replicate necessary paracrine signaling in cell products? What is the optimal ratio of alpha and beta cells in a cell product for function? Does the physical orientation and connection of these cells within a cell graft impact transplant function? To address these questions, we need the ability to test cell products with defined composition. Recent advances by our lab have made this type of analysis possible. This project will evaluate the function of cell products with varying composition of alpha and beta cells to find the optimal ratio and organization of these cells.
Description of Project
Cell therapies for type 1 diabetes (T1D) hold the promise of a functional cure for those living with this disease. Although current therapies are advancing, many questions regarding the optimal composition of cell therapies remain unknown. This proposal will aim to understand the impact of differing cell ratios within graft products with particular focus on insulin producing beta cells and glucagon producing alpha cells. The results of these studies will allow for the generation of improved cell products that are better able to regulate blood glucose levels in patients.
Anticipated Outcome
The anticipated outcomes of this project could significantly improve the treatment of Type 1 diabetes (T1D). By developing new cell-based therapies using stem cells, we expect to find the best way to combine insulin-producing cells (beta cells) and glucagon-producing cells (alpha cells) to better regulate blood sugar levels. This approach could lead to more effective and long-lasting treatments, potentially reducing or eliminating the need for daily insulin injections.
We also expect to gain important insights into how these cells interact with each other in a transplant, helping us understand how to mimic the natural function of the pancreas more closely. If successful, this research could bring us closer to a functional cure for T1D, offering people with the condition a more natural and stable way to control their blood sugar and prevent long-term complications.
Relevance to T1D
This project is highly relevant to T1D because it focuses on developing a new approach to treatment that could replace damaged cells with healthy ones, using stem cells. By creating insulin-producing beta cells and glucagon-producing alpha cells from stem cells, and studying how to combine them most effectively, this research aims to restore normal blood sugar control in people with T1D. If successful, this approach could provide a longer-lasting and more natural solution, potentially reducing or even eliminating the need for insulin injections.