Cardiac Mesenchymal Cells from Failing and Non-Failing Hearts Limit Ventricular Dilation when Administered Late after Infarction

Although cell therapy-mediated cardiac repair offers promise for treatment/management of heart failure, lack of fundamental understanding of how cell therapy works limits its translational potential. In particular, whether reparative cells from failing hearts differ from cells derived from non-failing hearts remains unexplored. Here, we assessed differences between cardiac mesenchymal cells (CMC) derived from failing (HF) versus non-failing (Sham) hearts and whether the source of donor cells (i.e., from HF vs Sham) limits reparative capacity, particularly when administered late after infarction. To determine the impact of the donor source of CMCs, we characterized the transcriptional profile of CMCs isolated from sham (Sham-CMC) and failing (HF-CMC) hearts. RNA-seq analysis revealed unique transcriptional signatures in Sham-CMC and HF-CMC, suggesting that the donor source impacts CMC. To determine whether the donor source affects reparative potential, C57BL6/J female mice were subjected to 60 min of regional myocardial ischemia, then reperfused for 35 d. In a randomized, controlled, and blinded fashion, vehicle, HF-CMC, or Sham-CMC were injected into the lumen of the left ventricle at 35 d post MI. An additional five weeks later, cardiac function was assessed by echocardiography, which indicated that delayed administration of Sham-CMC and HF-CMC attenuated ventricular dilation. We also determined whether Sham-CMC and HF-CMC treatments affected ventricular histopathology. Our data indicate that the donor source affects certain aspects of CMC and these insights may have implications for future studies. Our data indicate that delayed administration of CMC limits ventricular dilation, and that the source of CMC may influence their reparative actions.