Transplantation of iPSc Restores Cardiac Function by Promoting Angiogenesis and Ameliorating Cardiac Remodeling in a Post-infarcted Swine Model.

Abstract

Induced pluripotent stem cells (iPSc) hold significant promise for the development of cardiac regenerative therapy for myocardial infarction (MI). However, preclinical optimization and validation of large-animal models will be required before iPSc used clinically. Therefore, we aim to investigate the therapeutic potential of iPSc transplantation for MI and relative mechanisms in a post-infarcted swine model. Left anterior descending coronary artery was balloon-occluded after percutaneous transluminal angiography to generate MI (60-min no-flow ischemia). Animals were then divided into Sham, PBS control, and iPS experimental groups. The cardiac function and LV structural were assessed by dual-source computed tomography. Terminal deoxynucleotidyl nick end labeling, histology, and immunofluorescence were used to examine the effect of transplanted iPS cells on apoptosis, fibrosis, and hypertrophy. At 6 weeks, LV structural abnormality and cardiac dysfunction were less pronounced in iPSc group than in PBS group, and these improvements were accompanied by reduction of scar size. iPSc transplantation was associated with significant increase of vascular density and reduced myocardial apoptosis in the border zone of infarction, which was accompanied by the reduction in fibrosis degree. Moreover, proangiogenic and antiapoptotic factors were increased significantly in iPS group compared with PBS group. Cardiomyocyte hypertrophy was significantly attenuated by iPSc transplantation. In conclusion, these results suggested that transplantation of iPSc may result in functional recovery by promoting angiogenesis, inhibiting apoptosis, and ameliorating cardiac remodeling. This proof of concept study may provide a basis for an autologous iPSc-based therapy of MI.