The University of Pittsburgh has developed a way to use an adenovirus, a modified cold virus, to deliver growth factor genes to islets in vitro. This could supply virtually unlimited amounts of growth factor to every islet cell. The project will also explore how well the islets that receive the growth factors function once they are transplanted into diabetic rodents. Top Improving Tolerance Principal Investigator - John Fung, MD, PhD One of the challenges facing physicians attempting to transplant normal functioning islets into Type 1 diabetes patients is finding a way to overcome the normal defenses against foreign tissues that the human body turns on whenever a transplant takes place, also known as the alloimmune response. Dr. Fung and co-workers will explore whether the alloimmune response can be moderated by genetically altering dendritic cells, which originate in bone marrow.
Dendritic cells act as gate keepers in the body's immune response process.
They capture antigens, present them to T and B cells and signal the T and B cells whether or not the antigens should be considered as foreign. If the dendritic cells present the antigens as foreign, the T and B cells begin to destroy the invaders. This project will try to genetically alter the dendritic cells so that they no longer signal T and B cells to attack transplanted islets. The project builds on the long-standing research being done at the University of Pittsburgh on chimerism the coexistence of donor and recipient cells in transplant patients. These findings suggest that long-lived donor cells may help facilitate acceptance of transplanted organs, known as tolerance.