Introduction: Stem cells are being tested in clinical trials for cardiac repair. Bone marrow derived allogeneic (unrelated donor) mesenchymal stem cells and induced pluripotent stem cells (iPSC) have emerged as ideal cell types for cardiac repair and regeneration. Outcome of initial allogeneic stem cells based clinical trials was positive. There were no significant side effects observed after cell transplantation. In fact, the implanted cells were able to improve cardiac function. However, poor survival of transplanted cells in the myocardium is a major hurdle in clinical translation of stem cell-based therapies for cardiac repair.
Methods: We have previously reported that after transplantation in the ischemic heart stem cells display immunogenicity and are rejected by recipient immune system. In our ongoing studies, we have been engaged in developing immunomodulatory biomaterials-based strategies to prolong survival of transplanted stem cells in the heart. We synthesized MXene quantum dots (MQDs) with tailored surface properties to possess intrinsic immunomodulatory properties.
Results and conclusion: Our data demonstrate that MQDs were spontaneously uptaken into antigen-presenting cells and downregulated the expression of genes involved in alloantigen presentation, and consequently reduced the activation of allogeneic lymphocytes. Furthermore, MQDs are able to selectively reduce activation of CD4+IFN-γ+ T-lymphocytes and promote expansion of immunosuppressive CD4+CD25+FoxP3+ regulatory T-cells in a stimulated human lymphocyte population. Furthermore, MQDs are biocompatible with MSCs and iPSC. Next, MQDs were incorporated 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. These findings suggest that this new class of biomaterials may bridge the translational gap in stem cells and biomaterials-based strategies for cardiac tissue engineering.