Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis

Abstract

Mesenchymal stem cells (MSCs) are pluripotent cells that differentiate into a variety of cells, including cardiomyocytes and endothelial cells. However, little information is available regarding the therapeutic potency of systemically delivered MSCs for myocardial infarction. Accordingly, we investigated whether intravenously transplanted MSCs induce angiogenesis and myogenesis and improve cardiac function in rats with acute myocardial infarction. MSCs were isolated from bone marrow aspirates of isogenic adult rats and expanded ex vivo. At 3 h after coronary ligation, 5 x 10(6) MSCs (MSC group, n=12) or vehicle (control group, n=12) was intravenously administered to Lewis rats. Transplanted MSCs were preferentially attracted to the infarcted, but not the noninfarcted, myocardium. The engrafted MSCs were positive for cardiac markers: desmin, cardiac troponin T, and connexin43. On the other hand, some of the transplanted MSCs were positive for von Willebrand factor and formed vascular structures. Capillary density was markedly increased after MSC transplantation. Cardiac infarct size was significantly smaller in the MSC than in the control group (24 +/- 2 vs. 33 +/- 2%, P <0.05). MSC transplantation decreased left ventricular end-diastolic pressure and increased left ventricular maximum dP/dt (both P <0.05 vs. control). These results suggest that intravenous administration of MSCs improves cardiac function after acute myocardial infarction through enhancement of angiogenesis and myogenesis in the ischemic myocardium.

Mesenchymal stem cells are superior to angiogenic growth factor genes for improving myocardial performance in the mouse model of acute myocardial infarction

“…Most of the cell therapies using MSCs for myocardial infarction are of isogenic or allogenic origins [26,27]. Rare studies used the human MSCs to treat myocardial infarction in mice model.…”

Potential of mesenchymal stem cells in gene therapy approaches for inherited and acquired diseases

“…Toma et al in an earlier study showed that human MSCs when injected directly into the myocardium of mice can differentiate into cardiomyocytes expressing the cardiac markers, desmin, β-myosin heavy chain, α-actinin, cardiac troponin T and phospholamban at levels comparable to those of the host cardiomyocytes [77]. In a rat model of acute myocardial infarction, Nagaya et al showed that rats that were transplanted intravenously with MSCs had improved cardiac function through enhancement of angiogenesis and myogenesis in the ischaemic myocardium compared to the control group [78]. These MSCs were isolated from BM aspirates of isogenic adult rats and expanded ex vivo.…”

Efficacy and Safety of Intracoronary Autologous Bone Marrow‐Derived Cell Transplantation in Patients With Acute Myocardial Infarction: Insights From Randomized Controlled Trials With 12 or More Months Follow‐Up

“…Experimental studies indicated that bone marrow-derived cells (BMC) could differentiate to cardiomyocytes and an intramyocardium injection of BMC improved cardiac function after an acute MI. 1,2 Recent clinical trials and meta-analyses also showed that intracoronary Chunyu Zhang, MD and Aijun Sun, PhD contributed equally to this work. autologous BMC transfer after acute MI modestly improved left ventricular ejection fraction (LVEF) and significantly reduced left ventricular end-systolic volume (LVESV) and infarct size after acute MI within 12 months post BMC transplantation.…”