The Origin of Human Mesenchymal Stromal Cells Dictates Their Reparative Properties

Abstract

Background Human mesenchymal stromal cells ( hMSC s) from adipose cardiac tissue have attracted considerable interest in regard to cell‐based therapies. We aimed to test the hypothesis that hMSC s from the heart and epicardial fat would be better cells for infarct repair. Methods and Results We isolated and grew hMSC s from patients with ischemic heart disease from 4 locations: epicardial fat, pericardial fat, subcutaneous fat, and the right atrium. Significantly, hMSC s from the right atrium and epicardial fat secreted the highest amounts of trophic and inflammatory cytokines, while hMSC s from pericardial and subcutaneous fat secreted the lowest. Relative expression of inflammation‐ and fibrosis‐related genes was considerably higher in hMSC s from the right atrium and epicardial fat than in subcutaneous fat hMSC s. To determine the functional effects of hMSC s, we allocated rats to hMSC transplantation 7 days after myocardial infarction. Atrial hMSC s induced greatest infarct vascularization as well as highest inflammation score 27 days after transplantation. Surprisingly, cardiac dysfunction was worst after transplantation of hMSC s from atrium and epicardial fat and minimal after transplantation of hMSC s from subcutaneous fat. These findings were confirmed by using hMSC transplantation in immunocompromised mice after myocardial infarction. Notably, there was a correlation between tumor necrosis factor‐α secretion from hMSC s and posttransplantation left ventricular remodeling and dysfunction. Conclusions Because of their proinflammatory properties, hMSC s from the right atrium and epicardial fat of cardiac patients could impair heart function after myocardial infarction. Our findings might be relevant to autologous mesenchymal stromal cell therapy and development and progression of ischemic heart disease.