Abstract 20592: Allogeneic c-kit+ Cardiac Progenitor Cells are Hypoimmunogenic and Improve Cardiac Function
Background: Autologous c-kit+ cardiac progenitor cells (c-kit+ CPCs) and cardio-sphere derived cells (CDCs) were reported to be effective in reducing scar size in myocardial infarction patients. We have recently identified that c-kit+ CPCs have superior cardiac regenerative potentials over CDCs, independent of patient specific characteristics. However, c-kit+ CPCs allogeneic potentials were not been investigated. In this study we compared c-kit+ CPCs in vitro and in vivo immunological tolerance and in vivo cardiac recovery potentials using divergent rat strains.
Methods and Results: We isolated human c-kit+ CPCs (hc-kit+ CPCs), hCDCs from adult coronary artery bypass graft patients and compared with human mesenchymal stem cells (hMSCs). Human c-kit+ CPCs, CDCs and MSCs expressed major histocompatibility complex (MHC) I but not MHC II and co-stimulatory molecules (CD80 and CD86). In mixed lymphocyte reaction (MLR) assay, co-culture of human peripheral blood monocytes with allogeneic hc-kit+ CPCs, hCDCs and hMSCs elicit negligible T-cell proliferation. To further understand the allogeneic potentials of c-kit+ CPCs, Wistar Kyoto (WKY) rat c-kit+ CPCs (rc-kit+ CPSs) and MSCs (rMSCs) were isolated and evaluated their alloantigen expression, which shows similar pattern as human c-kit+ CPCs and MSCs. Co-culture of rc-kit+ CPCs and rMSCs with Brown Norway (BN) rat lymphocytes failed to induce proliferation of T-cells, which is similar to syngeneic rc-kit+ CPCs and allogeneic rMSCs. In vivo, intra-myocardial transplantation of allogeneic c-kit+ CPCs recover the cardiac function of myocardial infarction rats. In addition, allogeneic and syngeneic c-kit+ CPCs elicit minimal local, systemic and humoral immune responses compared to xenogeneic c-kit+ CPCs.
Conclusion: Human and rat allogeneic c-kit+ CPCs are immune tolerant and produce minimal immunological response while maintaining their cardiac recovery potentials in immunologically divergent species. Our observations warrant the development of an allogeneic c-kit+ CPC strategy for clinical trail application.
Author Disclosures: S. Datla: None. Y. Guo: None. R. Mishra: None. L. Chan: None. G. Bigham: None. G. Jack: None. A. Garzino-Demo: None. S. Kaushal: None.
- © 2016 by American Heart Association, Inc.