Abstract: Donor derived allogeneic stem cells including mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs) are being tested in animal studies and clinical trials for cardiac regeneration and repair. The outcome of initial studies was very encouraging and transplanted cells were safe in the recipient heart. However, poor survival of transplanted stem cells in the infarcted heart has impaired the clinical translation of stem cells-based therapies. We have performed investigations to understand the mechanisms of poor survival of implanted stem cells in the heart. We found that allogeneic stem cells after transplantation in the ischemic heart turned immunogenic and were subsequently rejected by host immune system. In our ongoing studies we are focusing on understanding the mechanisms of increase in immunogenicity of allogeneic stem cells. We are also developing biomaterials-based strategies to prevent rejection of transplanted cells in the heart. We synthesized and characterized MXene quantum dots (MQDs). MQDs possess intrinsic immunomodulatory properties and selectively reduce activation of CD4+IFN-γ+ T-lymphocytes and promote expansion of immunosuppressive CD4+CD25+FoxP3+ regulatory T-cells in an activated lymphocyte population. We also incorporated MQDs into a chitosan-based hydrogel to create a 3D platform for stem cell delivery to the heart. This composite immunomodulatory hydrogel-based platform improved survival of stem cells and mitigated allo-immune responses. We also found that MQDs have potential to mitigate allograft vasculopathy and prevent rejection of transplanted organs. These studies highlight the potential of MXene based next generation biomaterials for cardiac regenerative medicine.
About the speaker: Dr. Sanjiv Dhingra is a Professor at the University of Manitoba, Director of Canada Italy Tissue Engineering Program Institute of Cardiovascular Sciences and a researcher at St. Boniface Hospital Research Regenerative Medicine Program. He is a Professor at the Department of Physiology and Pathophysiology, Biomedical Engineering Program Max Rady College of Medicine, Rady Faculty of Health Sciences University of Manitoba.