Performed at the DRI since the 1980s, successful islet cell transplants give patients with type 1 diabetes (T1D) the ability to naturally produce their own insulin and lead healthier, more independent lives. However, only a small number of patients benefit from the procedure because of a shortage of cadaver islets, problems associated with the need for chronic immunosuppression drugs, and the low survival rate of islets immediately following implantation. The current transplant site, the liver, can be particularly inhospitable for newly implanted islets, leading to hypoxia (low oxygen) and inflammation. The number of transplants available to patients is also limited by the small number of donors and the large number of cells required for each procedure.
In the $4.6 million grant proposal being funded jointly by the JDRF-Helmsley Charitable Trust over three years, Dr. Ricordi's team will attempt to address the limitations of the requirements for immunosuppression, and the poor viability of islets, beginning with an alternate site of implantation. While the research community is exploring multiple possible alternatives, the DRI has chosen to pursue a fold in the lining of the abdomen called the omentum that the team believes will allow better access for the procedure, offer more space to accommodate delivery systems, and provide a safer environment for the newly-implanted cells.
"This is a critically important and timely support that will allow our team to remain focused on the path to a biologic cure for diabetes," Dr. Ricordi said. "The overall goal is to use a multipronged approach to address and resolve all of the outstanding issues in islet transplantation and move the field to the next level of success."
The other problem that Dr. Ricordi's team is attempting to solve is protecting the implanted cells from the body's immune response. Their approach to immunoprotection is two-fold. They will use a bioactive scaffold as a delivery system for the implanted islets that is designed to protect them from the immediate immune response. The scaffold allows the islet cells access to the surrounding blood vessels to prevent poor oxygenation, which will allow better regulation of blood sugar levels. The team is also engineering a conformal coating to encapsulate each islet to further promote long-term survival. Ultimately, the scaffold could be used to modify the immune cells in the implant local area, offering maximum protection. If successful, such technologies could remove the need for immunosuppression drugs and ensure long-term survival for the implanted cells.
"We are very excited to be supporting Dr. Ricordi's lab for this research," said JDRF Chief Scientific Officer Dr. Richard Insel. "Dr. Ricordi and colleagues have been pioneers in the area of islet cell transplantation and encapsulation, and we feel that they are well-positioned to advance an area that we hope will bring a real benefit to individuals with type 1 diabetes."
Provided by JDRF
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