Objective
The objective of this proposal is to develop a manufacturing process to produce a large quantity of stem cell-derived islets that could be shared with the research and clinical communities.
Background Rationale
We have developed a method to efficiently produce islet-like cells from stem cells (SC-islets), however our process would need to be automated and scaled up to be able to generate large number of cells for preclinical and clinical studies. Here, we plan to build of our findings to develop a scaled up process to generate SC-islets.
Description of Project
Type 1 Diabetes (T1D) is an autoimmune disorder that destroys insulin-producing pancreatic beta cells, resulting in insulin deficiency and chronic elevated blood sugar levels. As a result, people living with T1D are dependent and burdened from the need of life-long exogenous insulin administration, while suffering from severe complications. Whole pancreas or islet transplantation can, in some cases, eliminate the need for insulin injections, and drastically improve their quality of life. However, the shortage of suitable donors and the requirement for chronic immunosuppression both present challenges for this therapy's widespread use.
Multiple research groups have developed different methods to generate islet-like cells containing insulin producing cells from human pluripotent stem cells (hPSC), which could eliminate the problems associated with donor shortages. However, the generation of these cells is inefficient and costly and will require scaled-up production to ensure sufficient numbers of SC-islets are available to the research and clinical communities, and ultimately to patients suffering from T1D.
Consequently, the availability and application of SC-islets have been limited to a small number of research groups globally. We have optimized a protocol to produce high-quality, high-yield SC-islets, addressing these limitations. To facilitate the broader use of these cells in research and clinical studies, we set out to develop process to produce SC-islets in large scale, ensuring reproducibility, and accessibility. By establishing a reliable supply of SC-islets for the research community, this project will support advancements in type 1 diabetes research and potential therapies.
Anticipated Outcome
The activities outlined in this aim will create a platform to manufacture SC-islets for research, preclinical development and clinical studies, which will help to speed up the transition of discoveries into clinical applications and commercial products, available to patients.
Relevance to T1D
Type 1 diabetes (T1D) is an autoimmune disease where the body's immune system attacks and destroys the insulin-producing cells in the pancreas, leading to a severe lack of insulin. Over the past century, the discovery of insulin, along with technological advances have greatly improved life for people with T1D. Despite these improvements, managing the disease can still be very challenging, both physically and emotionally, for many people. The ultimate goal in treating type 1 diabetes (T1D) is to replicate the natural actions of the pancreas, producing insulin in a way that keeps blood sugar levels stable within a healthy range. Although pancreas and islet transplants can achieve this, they aren’t widely available due to a shortage of donors and the need for lifelong immunosuppressive drugs. Advances in creating insulin-producing cells from human pluripotent stem cells, along with genetic and bioengineering technologies, could help fill this gap. These approaches offer a potentially unlimited supply of cells for transplantation, possibly without the need for immunosuppressive drugs. Early clinical trials using stem cell-derived islet-like cells have shown that achieving insulin independence is possible. However, high costs associated with producing these cells limit their clinical availability and hinder the development of drug testing platforms. To speed up clinical applications, the manufacturing process for these cells needs improvement to make them more accessible for both research and treatment purposes.