{REDACTED} California Team Planning for Rapid Translation of Mesenchymal Stem Cell (MSC)-based Research to Advance Islet Transplantation for Treatment of Type 1 Diabetes

Funding Type: 
Disease Team Planning
Grant Number: 
DT1-00679
Investigator: 
ICOC Funds Committed: 
$0
Public Abstract: 
It is estimated that 1 out of 7 California (CA) residents has diabetes or is at high risk of developing the disease. Up to 10% (500,000) are thought to have or be at risk for type 1 diabetes (T1D). T1D is an autoimmune disease that destroys insulin producing cells. Patients with T1D must take insulin injections to survive. Even with insulin, it is difficult to achieve good blood sugar control, which can lead to devastating complications, including heart disease, blindness, limb amputation, and kidney failure. A quarter of the Medicare budget is spent on diabetes-related care, which is a financial burden to State and Federal health care programs, and the taxpayers who support them. Islet transplant improves blood sugar control and allows T1D patients to stop taking insulin shots. Unfortunately, recipients must take immunosuppression drugs to prevent rejection of the donor cells. Immunosuppression increases the risk of infection and causes other side effects. Due to these risks, only patients with very severe diabetes are eligible to receive islet transplant. Even with immunosuppression, islets are inadequately protected and lose function with time. This project seeks to improve long-term islet transplant results and eliminate the need for long-term immunosuppression by inducing a state of immune system acceptance of the transplanted donor islets using mesenchymal stem cells (MSCs) from the same donor. MSCs are cells in the bone marrow that are capable of differentiating into various cell types and have immune inhibitory effects. In rats, we have successfully reversed diabetes with co-transplantation of MSCs, bone marrow cells, and islets taken from an unrelated donor animal without the need for long-term immunosuppression. We now seek to test this approach in large animals and expect to be ready for clinical studies within 5 years. This will be accomplished through a strong team-based approach of collaboration among clinicians and scientists throughout CA, as well as with outside collaboration with national experts in the field. This grant will provide funds needed to assemble and coordinate a diverse team to effectively manage the progression of this research from the lab to bedside. Induction of immune tolerance using MSCs stands to drastically improve treatment for the hundreds of thousands of T1D patients in CA and millions of patients worldwide. This approach, along with strategies to increase islet supply, may make it possible to treat patients with other forms of diabetes with islet transplant and could potentially improve transplantation of organs, tissues or stem cell products for the treatment of other chronic illnesses. Improving blood sugar control with stable islet transplants may also reduce diabetes complications, reducing the drain on State and Federal medical programs. CA, with its many leading medical centers and research programs is uniquely qualified to facilitate the advancement of this approach.
Statement of Benefit to California: 
It is estimated that 1 out of 7 California (CA) residents has diabetes or is at high risk of developing the disease. Up to 10% (500,000) are thought to have or be at risk for type 1 diabetes (T1D). T1D is an autoimmune disease that destroys insulin producing cells. Patients with T1D must take insulin injections to survive. Even with insulin, it is difficult to achieve good blood sugar control, which can lead to devastating complications, including heart disease, blindness, limb amputation, and kidney failure. A quarter of the Medicare budget is spent on diabetes-related care, which is a financial burden to State and Federal health care programs, and the taxpayers who support them. Islet transplant improves blood sugar control and allows T1D patients to stop taking insulin shots. Unfortunately, recipients must take immunosuppression drugs to prevent rejection of the donor cells. Immunosuppression increases the risk of infection and causes other side effects. Due to these risks, only patients with very severe diabetes are eligible to receive islet transplant. Even with immunosuppression, islets are inadequately protected and lose function with time. This project seeks to improve long-term islet transplant results and eliminate the need for long-term immunosuppression by inducing a state of immune system acceptance of the transplanted donor islets using mesenchymal stem cells (MSCs) from the same donor. MSCs are cells in the bone marrow that are capable of differentiating into various cell types and have immune inhibitory effects. In rats, we have successfully reversed diabetes with co-transplantation of MSCs, bone marrow cells, and islets taken from an unrelated donor animal without the need for long-term immunosuppression. We now seek to test this approach in large animals and expect to be ready for clinical studies within 5 years. This will be accomplished through a strong team-based approach of collaboration among clinicians and scientists throughout CA, as well as with outside collaboration with national experts in the field. This grant will provide funds needed to assemble and coordinate a diverse team to effectively manage the progression of this research from the lab to bedside. Induction of immune tolerance using MSCs stands to drastically improve treatment for the hundreds of thousands of T1D patients in CA and millions of patients worldwide. This approach, along with strategies to increase islet supply, may make it possible to treat patients with other forms of diabetes with islet transplant and could potentially improve transplantation of organs, tissues or stem cell products for the treatment of other chronic illnesses. Improving blood sugar control with stable islet transplants may also reduce diabetes complications, reducing the drain on State and Federal medical programs. CA, with its many leading medical centers and research programs is uniquely qualified to facilitate the advancement of this approach.

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