Mesenchymal Stem Cells in Autograft Fibrosis

Chronic rejection is a serious complication of organ transplantation, even in the presence of immunosuppression. Chronic rejection typically results in fibrosis of the graft--the laying down of excess extra cellular matrix until the organ becomes dysfunctional. Despite the widely appreciated magnitude of the problem and the numerous research efforts to control it, effective therapies to control allograft fibrosis are lacking. Fibroblasts are the sole cell type that forms the scar tissue that eventually leads to the dysfunction of the transplanted organs. The mechanisms that control the recruitment, differentiation, and proliferation of intragraft fibroblasts are poorly understood. Recent data have suggested that proliferating intragraft fibroblasts are derived from transplant recipients. New findings indicate that mesenchymal stem cells (MSC) play an important role in the development of allograft fibrosis. The long-term goals of the research program are to apply genetic and cellular therapies for chronic rejection of solid organ transplants.