Intramyocardial Transplantation of Human iPS Cell-Derived Cardiac Spheroids Improves Cardiac Function in Heart Failure Animals

JACC Basic Transl Sci. 2021 Feb 19;6(3):239-254. doi: 10.1016/j.jacbts.2020.11.017. eCollection 2021 Mar.


The severe shortage of donor hearts hampered the cardiac transplantation to patients with advanced heart failure. Therefore, cardiac regenerative therapies are eagerly awaited as a substitution. Human induced pluripotent stem cells (hiPSCs) are realistic cell source for regenerative cardiomyocytes. The hiPSC-derived cardiomyocytes are highly expected to help the recovery of heart. Avoidance of teratoma formation and large-scale culture of cardiomyocytes are definitely necessary for clinical setting. The combination of pure cardiac spheroids and gelatin hydrogel succeeded to recover reduced ejection fraction. The feasible transplantation strategy including transplantation device for regenerative cardiomyocytes are established in this study.

Keywords: CM, cardiomyocyte; CMR, cardiac magnetic resonance; CS, cardiac spheroid; ECG, electrocardiogram; EF, ejection fraction; FAC, fractional area change; GH, gelatin hydrogel; HF, heart failure; LV, left ventricular; LVEDV, left ventricular end-diastolic volume; LVESV, left ventricular end-systolic volume; VEGF, vascular endothelial growth factor; cardiac spheroids; cardiomyocyte; cell transplantation; dp/dtmax, maximum rate of left ventricular pressure rise; hPSC, human pluripotent stem cell; heart failure; hiPSC, human induced pluripotent stem cell; human iPS cells; sCM, single cardiomyocyte.