Therapeutic benefits of CD90‐negative cardiac stromal cells in rats with a 30‐day chronic infarct

Abstract

Cardiac stromal cells (CSCs) can be derived from explant cultures, and a subgroup of these cells is viewed as cardiac mesenchymal stem cells due to their expression of CD90. Here, we sought to determine the therapeutic potential of CD90‐positive and CD90‐negative CSCs in a rat model of chronic myocardial infarction. We obtain CD90‐positive and CD90‐negative fractions of CSCs from rat myocardial tissue explant cultures by magnetically activated cell sorting. In vitro, CD90‐negative CSCs outperform CD90‐positive CSCs in tube formation and cardiomyocyte functional assays. In rats with a 30‐day infarct, injection of CD90‐negative CSCs augments cardiac function in the infarct in a way superior to that from CD90‐positive CSCs and unsorted CSCs. Histological analysis revealed that CD90‐negative CSCs increase vascularization in the infarct. Our results suggest that CD90‐negative CSCs could be a development candidate as a new cell therapy product for chronic myocardial infarction.

Characterization of Human Cardiac Mesenchymal Stromal Cells and Their Extracellular Vesicles Comparing With Human Bone Marrow Derived Mesenchymal Stem Cells

“…＋ cells, and histological analysis of CD90 − cells revealed an increase in vascularization within the infarct lesion (12). Other studies reported similar salutary effects, since CD90…”

“…− CDCs over CD90 ＋ CDCs (9,11,12). In the chronic MI rat model, injection of CD90 − CMSCs augmented cardiac function outperforming CD90…”

“…＋ cells, and both CD90 − and CD90 ＋ CMSCs secrete VEGF or basic fibroblast growth factor (bFGF) comparably (12). By means of the transcriptional profiles and gene ontology enrichment analysis of adult human CDCs subdivided by the expression of CD90, CD90…”

“…The expression of GATA4 was detected only in CMSCs. ing CD90 in CVR, several studies proved that CD90 − CPCs expressed the genes related to stemness and could differentiate into mature cardiomyocytes with complete sarcomere formation (9,11,12). Although these cells also showed a greater regenerative potential in myocardial infarction (MI), it is still unclear which types of CS/CPCs are more important to the CVR.…”

Empagliflozin reduces the senescence of cardiac stromal cells and improves cardiac function in a murine model of diabetes

“…Cardiac stromal cells (CSC) are a heterogeneous population of non‐cardiomyocyte CD45‐, CD34‐, CD31‐ and CD105+ cells including fibroblasts, resident in the heart with supportive and paracrine functions. The crosstalk between cardiomyocytes and CSC plays a fundamental role for the repair processes after cardiac damage, through the release of growth factors, pro‐angiogenic factors and the regulation of cardiac metabolism 4‐6 . Over and above normal cellular ageing, exposure to cardiovascular risk factors accelerates the senescence of cardiomyocytes and CSC, hampering their cardioprotective and repairing functions, and ultimately leading to HF 7 .…”