Abstract 18207: The Efficacy of Transplantation of Human Ips Cell Derived Cardiac Tissue for Dilated Cardiomyopathy Hamster Model
Introduction: Cardiovascular disease remains a major cause of death despite advances in medical technology. Induced pluripotent stem cells (iPSCs) are a potential resource of cardiac regenerative therapy which can theoretically provide large number of cardiovascular cell populations. We previously reported that a cell sheet format reassembled from human iPSC-derived cardiovascular cell populations including cardiomyocytes and vascular cells (Cardiac Tissue Sheet; CTS) promotes cardiac regeneration and functional recovery for a rat myocardial infarction model (Sci Rep, 2014). Human iPSC-derived Cardiac Tissue (HiCT) made by multiple stacking using gelatin hydrogel microspheres (GHMs) further reinforce the advantageous effects (Sci Rep, 2015). Dilated Cardiomyopathy (DCM) is a clinical set of heart diseases which manifests congestive heart failure or sudden death, causing high morbidity and mortality throughout the world. Here we aimed to validate the therapeutic ability of HiCT for this pathology.
Methods&Results: Male 20-week old J2N-k hamsters which exhibit DCM-like phenotype were used as recipients of HiCT. We differentiated human iPSCs into cell populations including cardiomyocytes, endothelial cells, and vascular mural cells by a monolayer high-density culture method, and then replated them to temperature-responsive culture dishes (UpCell; CellSeed, Tokyo, Japan) to generate CTSs. We stacked the CTSs using GHMs up to 5 layers (HiCT-5) and transplanted them to DCM hearts. Echocardiography demonstrated striking effects of the HiCT-5 which significantly attenuated LV dilatation compared to that in sham group [diastolic diameter of left ventricle at 4 weeks after surgery: sham vs transplantation, 0.65±0.01 (n=10) vs 0.61±0.01% (n=5) , P<0.001; 12 weeks after surgery: 0.75±0.02 (n=9) vs 0.67±0.02cm (n=3), P<0.001] and ameliorated LV systolic dysfunction (fractional shortening at 4 weeks after surgery: 24.5±1.0 vs 32.6±3.3%, P<0.001; 12 weeks after surgery: 17.3±0.8 vs 23.6±1.1%, P<0.001) which were a natural course in non-treated DCM hamsters which exhibited time-dependent deterioration.
Conclusions: Transplantation of HiCT may lead to functional restoration in DCM hearts.
Author Disclosures: S. Takimoto: None. H. Masumoto: None. K. Minakata: None. Y. Tabata: None. J.K. Yamashita: None.
- © 2016 by American Heart Association, Inc.