Objective
This study aims to create modified stem cells that produce insulin and can avoid detection by the immune system, reducing the need for immune suppressing drugs. This approach aims to offer a safer, more effective treatment for type 1 diabetes by providing long-lasting, insulin-producing cells.
Background Rationale
T1D is a serious disease where the immune system mistakenly destroys the body’s insulin-producing cells. Without insulin, people with T1D must constantly monitor their blood sugar and rely on insulin injections, which don’t fully mimic the body’s natural control of blood sugar. A promising alternative is to replace the destroyed cells with lab-grown insulin-producing cells. However, a major challenge is that the immune system can also attack these replacement cells, requiring lifelong immune-suppressing drugs. This study aims to develop modified cells that can evade the immune system, offering a safer, more effective, and long-term solution for T1D treatment.
Description of Project
Type 1 diabetes (T1D) is a complex disease where the body’s immune system mistakenly attacks insulin-producing beta cells. Insulin regulates blood sugar, and those with T1D rely on lifelong insulin injections. However, even advanced medical treatments often fall short of normalizing blood sugar levels. Replacing lost beta cells is promising, yet finding enough donors and avoiding immune rejection are significant obstacles.
Researchers are transforming stem cells into insulin-producing beta cells, or stem cell-derived islets (SC-islets), offering a potential unlimited cell supply. However, the immune system sees these cells as foreign and attacks them. This is primarily caused by a set of proteins on cell surfaces, known collectively as the Major Histocompatibility Complex (MHC), which helps the immune system distinguish between the body’s own cells and foreign invaders. Traditionally, immune suppressing drugs protect transplants, but they have serious side effects. To avoid this, scientists are investigating ways to make SC-islet “invisible” to the immune system through “immune evasion.” By gene editing, researchers can modify SC-islet to avoid immune detection, potentially creating a universal source of SC-islet suitable for any T1D patient.
The study has three main aims: 1) Generate immune evasive stem cells by editing specific MHC genes; 2) Test various gene modifications to identify the most effective combinations; and 3) Monitor immune responses to evaluate cell survival in a large animal mode.
If successful, this research could transform diabetes care, enabling patients to receive functional SC-islet without immune suppression, thus eliminating the need for daily insulin. This large animal study is a vital step toward safe, effective, off-the-shelf therapies for people with T1D, potentially improving the lives of millions worldwide.
Anticipated Outcome
The anticipated outcome of this research is to create stem cells that can be transplanted without triggering an immune attack. By using specially modified stem cells that "hide" from the immune system, these new cells could restore natural insulin production without the need for lifelong immune-suppressing drugs. If successful, this approach could significantly improve the quality of life for people with diabetes, reducing daily insulin needs and the risks associated with current treatments. Ultimately, this research could bring us closer to a practical and long-lasting solution for managing and potentially curing type 1 diabetes.
Relevance to T1D
This research is highly relevant to type 1 diabetes as it seeks to develop long-lasting, insulin-producing cells that avoid immune rejection. By potentially replacing daily insulin injections with a one-time cell transplant, this approach could offer a safer, more effective way to manage and even reverse diabetes.