Mesenchymal stem cells in treating myocardial infarction

Mesenchymal stem cells (MSCs) have emerged as a highly promising strategy in regenerative medicine due to their self-renewal, pluripotency and immunomodulatory properties. MSCs are nonhematopoietic, multipotent stem cells that can differentiate into various mesodermal lineages and modulate the immune system. The therapeutic potential of MSCs from different tissues has been widely explored in preclinical models and clinical trials for human diseases, including myocardial infarction (MI). MI is a severe cardiovascular condition that often leads to myocardial damage and decreased cardiac function. MSCs may play a role in the treatment of MI through cell differentiation and paracrine effects. MSCs can differentiate into cardiomyocyte-like cells both in vitro and in vivo. In addition, MSCs can also differentiate into vascular lineages (e.g., vascular smooth muscle cells and endothelial cells). AD-MSCs have the potential to differentiate into contractible vascular smooth muscle-like cells under costimulation with TGF-β and bone morphogenetic protein-4 (BMP4).  Human BM-MSCs can differentiate into cells with endothelial cell phenotypic and functional characteristics in the presence of VEGF. Intravenously injected MSCs are capable of homing to the ischemic myocardium of rats, and the differentiation of MSCs into cardiomyocytes, smooth muscle cells, and endothelial cells can be observed from 1--4 weeks after transplantation. Although there is an enhancement in cardiac function following the transplantation of MSCs, evidence suggests that the engraftment and persistence of MSCs in areas of myocardial ischemia are neither substantial nor enduring. As a consequence, the functional benefits observed after MSC transplantation may be attributed to the release of soluble factors. MSCs can secrete VEGF, HGF, bFGF, IL-6, stromal cell-derived factor 1 (SDF-1), IGF-1, TGF-β, and PDGF for the treatment of MI. When cocultured with cardiomyocytes, BM-MSCs can release VEGF, bFGF, SDF-1, and IGF-1, which reduce hypoxia-induced apoptosis. Under hypoxia/reoxygenation conditions, human AD-MSCs upregulate the expression of several protective soluble factors (including HGF, VEGF-A, bFGF, and TGF-β) and inhibit the apoptosis of cardiomyocytes. In summary, MSCs could be a promising recent therapy for myocardial infarction and other diseases.

Dr. Tailin is an epidemiologist specializing in pharmacology, cerebrovascular and inflammatory diseases, and stem cell biology. He holds a PhD in Biology from Southern University of Science and Technology. He is currently the joint postdoctoral fellow in Chinese Academy of Sciences and the Second Affiliated Hospital of Southern University of Science and Technology. He currently leads several national research projects and has published 12 peer-reviewed papers in internationally renowned journals including Acta Pharmaceutica Sinica B, Bone Research, Cell Death and Differentiation, and Signal Transduction and Targeted Therapy over the past 5 years.