Grant: Project Grant

Heart disease is one of the leading causes of death in Canada. Unfortunately, there are no effective therapies available that can provide permanent solution to the problem. Identifying, new research approaches that can offer permanent therapies for this disease are needed. Patients with heart disease require constant long-term treatment and care. Therefore, it imposes a significant economic burden on Canadian healthcare system. The strategy of transplanting stem cells into damaged heart has emerged as a novel therapy for the treatment of heart disease as stem cells have the ability to transform into heart cells and replace dead cardiac cells. Bone marrow derived allogeneic (unrelated donor) mesenchymal stem cells (MSCs) from young healthy donors have emerged as ideal candidates for cardiac repair, because these cells have the ability to suppress the host immune system and survive in the heart after transplantation. Moreover, there are no ethical issues involved with these cells. However, recent reviews of animal studies and initial clinical trials reported that allogeneic MSCs were rejected by host immune system that impaired the benefits of allogeneic MSCs mediated therapy. Therefore, understanding the cell signaling pathways that regulate transplanted stem cell survival/rejection in the heart will help in developing new therapeutic agents that could prevent stem cell rejection and enhance the benefits of stem cell therapy. The objectives of current proposal are to study the mechanisms of transplanted stem cell rejection and to find out the strategies to increase post-transplantation survival in the heart. The outcome of this research will help in interpreting the results of ongoing allogeneic mesenchymal stem cell based clinical trials, and to carefully design future trials. The long-term objectives of this research are directed toward improving the quality of life of patients with heart disease using stem cell therapy.