Breakthrough: Double-Transplant Cures Type-1 Diabetes in Mice

An experiment has successfully cured type-1 diabetes in mice using a double-transplant method. This approach involved transplanting both islet cells and blood stem cells from a healthy mouse. The treated mice did not experience host rejection of one cell type and their immune systems did not attack the other, leading to a diabetes cure without observed side-effects.

Stanford University researchers, led by Seung Kim, MD, PhD, stated that the possibility of translating these findings into humans is significant.

The key steps, which create a hybrid immune system with cells from both donor and recipient, are currently used clinically for other conditions. Researchers believe this method could be transformative for individuals with type 1 diabetes, other autoimmune diseases, or those requiring solid organ transplants.

A Novel Double-Transplant Approach

Type-1 diabetes is an autoimmune disorder where the immune system attacks pancreatic islet cells, which produce insulin. In the study, type-1 diabetic mice received islet cells and blood stem cells from a healthy mouse. For six months, the treated mice required no insulin injections or medication to suppress graft-versus-host disease.

Addressing Type-1 Diabetes: The Dual Challenge

Pancreatic islet cells from the healthy donor present challenges as they are transplanted cells and are the target of the autoimmune disorder.

According to Dr. Kim, "addressing type-1 diabetes requires not only replacing lost islets but also resetting the recipient's immune system to prevent ongoing destruction." The creation of a hybrid immune system achieved both goals.

Key Steps and Remarkable Results

Using a pre-transplant preparatory drug, the combination of transplanted islet cells and hematopoietic stem cells established a mixed-origin immune system. This system prevented type-1 diabetes in all 19 treated mice and cured the disease in all 9 mice with long-term type-1 diabetes.

None of the cured mice needed insulin or immunosuppressants during the six-month follow-up.

Innovating Pre-Treatment Methods

A related discovery by Dr. Judith Shizuru involved developing a gentler pre-treatment method for blood stem cell transplantation. This procedure, previously used for certain cancers like leukemia and lymphoma, typically requires intense radiation therapy to clear the patient's bone marrow. Dr. Shizuru's less vigorous method, which only 'knocked back' bone marrow sufficiently, also proved successful in the mice.

Translating to Humans: Challenges and Future Directions

While promising for autoimmune diseases, the mouse model faces two challenges for human translation. Pancreatic islet cells are currently only obtainable from deceased donors, and blood stem cells must come from the same donor. Additionally, the required quantity of islet cells for humans remains undetermined due to size differences. Future research will focus on cultivating pancreatic islet cells in labs from pluripotent stem cells or improving their survivability.