Human iPSC cardiomyocyte patch transplantation modifies extracellular matrix and fibroblast behavior after myocardial infarction.

Myocardial infarction (MI) followed by chronic heart failure is the main cause of mortality of heart diseases. Although reparative cell transplantation therapies with pluripotent stem cell-derived cardiomyocytes (CMs) represent a promising therapeutic strategy, molecular mechanisms of the therapy remain elusive. Here, we show that transplantation of the human induced pluripotent stem cell (hiPSC)-derived CM patch onto the damaged heart after MI increases the ratio of collagen type I against collagen type III to modulate alignment of the collagen fibers at the infarcted zone. As a result, tissue elasticity of the heart is improved, and fibrosis at the remote zone is reduced. Mechanistically, we find that hiPSC-derived CM patches secrete TGF-β1, directly inducing collagen type I production in fibroblasts but not collagen type III. Our results suggest the direct effect of the transplanted CM patch on the cardiac fibroblasts to improve elasticity of the damaged heart, resulting in functional recovery after MI.