Abstract 16368: Establishment of Administration Protocol of Immunosuppressive Drug for Ips Cell Derived Cardiomyocytes Patch Transplantation in Rat Myocardial Infarction Model

Abstract

Background: Although Cardiomyogenesis therapy using iPS cells for heart failure should overcome immune rejection because of allogenic cell source, appropriate protocol of immunosuppressant to promise efficacy and safety has not been fully elucidated. In this study, we investigated the duration of immunosuppressant administration that could promise the efficacy of human iPS cell derived cardiomyocytes (hiPSCs-CM) patch transplantation as well as safety. Methods: The hiPSCs-CM patch were transplanted to myocardial infarction model rats with normal immune function in immunosuppressant treatment groups. Control were underwent sham operation and treated with no immunosuppressant (Group1). Immunosuppressant treatment groups were divided into three groups as follows: treated with tacrolimus (TAC), mycophenolate mofetil (MMF), and prednisolone (PSL) for 1month and 1 month tapering period (Group2); treated with TAC, MMF, and PSL for 2month and 1 month tapering period (Group3); and treated with TAC, MMF, and PSL for 3month and 1 month tapering period (Group4). After 6 months, cardiac function and histology were analyzed. Results: hiPSC-CM patch transplantation showed significant improvement cardiac fraction compared to the Group1 (ΔLVEF; Group2 22 ± 3 %, Group3 28 ± 5 %, Group4 23 ± 4 % versus Group1 -15 ± 8 %, P < 0.05) and did not show any differences in immunosuppressant treated groups. The hiPSCs-CM patch were detected for 2 months post-transplant and Improved Cardiac functions were maintained for at least 6 months despite disappearance of the transplanted patch. Fibrosis and cardiomyocyte size were significantly ameliorated in Group2-4 compared with Group1, however, there were significant differences in immunosuppressant treated groups. Furthermore, the Group 2, 3 and 4 showed a greater amount of structurally mature blood vessels compared with Group1, however, there were no significant in immunosuppressant treated groups. Tumor formation was not observed 6 months after transplantation in the Group 2, 3 and 4. Conclusion: 2 months administration of immunosuppressive agent may promise the safety and efficacy of hiPSCs-CM patch transplantation for rat ischemic heart failure model, proposing appropriate recipe of immunosuppressant in clinical trial.