Abstract 14554: Angiogenic Agent Ono-1301 Enhanced Cardiac Contractile Proteins in Hipsc Derived Cardiac Tissue-like Construct With Functional Angiogenesis

Abstract

Introduction: Transplantation of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) into myocardial infarcted areas has shown potential in healing myocardial infarction (MI). However, the survival rate of transplanted cells is yet considered limited, restricting the therapeutic effects of the transplantation. We assumed that adding angiogenic agent ONO-1301 could promote early stage angiogenesis between host and graft, and benefit the therapeutic effects of hiPSC-CM transplantation. Methods: This study is based on our former study of Cardiac Tissue-Like Construct (CTLC), where 5 x10e6 of hiPSC-CM was seeded on a 1x1cm poly(lactic-co-glycolic acid) (PLGA) nano fiber (Figure A). In addition, angiogenic agent ONO-1301 was mixed into the fibers. After 24h culture in vitro, 3 layers of CTLCs were transplanted into Nude rat MI models with or without ONO-1301. The rats were raised for another 4 or 8 weeks before sacrifice. Results: In vitro experiments have shown that supernatant of iPS-CM with ONO-1301 underwent a rise in VEGF during a 3 to 6 day culture (Figure B). The VEGF concentration in ONO-1301 positive group is much higer than ONO-1301 negative group (P=0.022) on day3. This difference narrows down over time. In vivo experiments on nude rat have shown that capillary density on MI border zone of ONO fiber+iPS-CM group is 29.95% higher than that of PLGA fiber+iPS-CM group (P=0.004) (figure C). HE and immunofluorescence staining shows remaining transplanted hiPSC-CMs in ONO fiber+iPS-CM group shows more significant TNT2 and human nuclear antigen(HNA) expression than that of PLGA fiber+iPS-CM group (Figure D and E). Also ONO fiber+iPS-CM group showed functional recovery compared to the sham.