Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Improve Cardiac Function and Reduce Scar Size Post MI

Abstract

Introduction/Aim: Mesenchymal stem cells (MSCs) have been shown to improve cardiac function after injury and are already being tested in clinical trials. The aim of this study is to test the cardiac regenerative potential of pluripotent stem cell (PSC)-derived MSC population to structurally and functionally repair the rat heart after myocardial infarction (MI) and to benchmark this efficacy to bone marrow (BM) derived MSCs that are already in the clinical trials stages. Methods: MI of athymic male rats was induced by 60 min of ischaemia-reperfusion (I/R) injury. Four days after I/R, animals were randomly assigned to one of the three treatment groups: (i) PSC-derived MSCs group (n = 4; (ii) BM-derived MSCs group (n = 3); (iii) Control group–media alone (n = 4). A total of 5 × 106 cells were injected at three sites within the left ventricular wall. TTE was performed at baseline on Day 4 (prior to cell injection) and Day 28. Animals were euthanised on Day 28, and hearts were harvested to assess for engraftment and extent of scar. Results: There was no evidence of cell engraftment using immunostaining at Day 28 in the BM MSCs and PSC-derived MSCs groups. TTE assessments of the infarcted rats at baseline and 1 month after cell injection showed a significant global increase of fractional shortening (FS) in the PSC-derived MSCs group (+5.5% of FS; p < 0.05). FS remained steady in the vehicle-injected hearts and decreased in the BM MSCs group (p = NS). There was also a reduction in scar size using PicroSirius Red staining in the PSC-derived MSCs treated group compared to the vehicle and BM-MSCs groups. Conclusion: PSC-derived MSCs show superiority over BM MSCs and vehicle in improving cardiac function 28 days after transplantation with reduction in scar size.