Myogenic Endothelial Cells Purified From Human Skeletal Muscle Improve Cardiac Function After Transplantation Into Infarcted Myocardium

Abstract

Objective The aim was to evaluate the therapeutic potential of human skeletal muscle-derived myoendothelial cells for myocardial infarct repair. Background We have recently identified and purified a novel population of myoendothelial cells from human skeletal muscle. These cells co-express myogenic and endothelial cell markers and produce robust muscle regeneration when injected into cardiotoxin-injured skeletal muscle. Methods Myoendothelial cells were isolated from biopsies of human skeletal muscle using a fluorescence-activated cell sorter along with populations of regular myoblasts and endothelial cells. Acute myocardial infarction was induced in male immune-deficient mice, and cells were directly injected into the ischemic area. Cardiac function was assessed by echocardiography, and donor cell engraftment, angiogenesis, scar tissue, endogenous cardiomyocyte proliferation and apoptosis were all evaluated by immunohistochemistry. Results A greater improvement in left ventricular function was observed after intramyocardial injection of myoendothelial cells when compared to hearts injected with myoblast or endothelial cells. Transplanted myoendothelial cells generated robust engraftments within the infarcted myocardium, and also stimulated angiogenesis, attenuation of scar tissue and proliferation and survival of endogenous cardiomyocytes more effectively than transplanted myoblasts or endothelial cells. Conclusions Our findings suggest that myoendothelial cells represent a novel cell population from human skeletal muscle that may hold promise for cardiac repair.

Perivascular Ancestors of Adult Multipotent Stem Cells

“…These cells exhibit a superior potential in sustaining cardiac function after acute myocardial infarction than myoblasts and endothelial cells. 7,54 The injection of myoendothelial cells significantly induced neoangiogenesis and reduced fibrosis in infarcted mouse hearts. 54 Pericytes, with their inherent actions on the vasculature 8 and recently documented multipotency, seem to match the scope of ideal cells for cardiac repair.…”

“…7,54 The injection of myoendothelial cells significantly induced neoangiogenesis and reduced fibrosis in infarcted mouse hearts. 54 Pericytes, with their inherent actions on the vasculature 8 and recently documented multipotency, seem to match the scope of ideal cells for cardiac repair. By using purified skeletal muscle pericytes, we designed a series of experiments to determine the potential of these cells for cardiac repair/regeneration.…”

Adult stem cells derived from skeletal muscle — biology and potential

“…After isolation, stem cells derived from skeletal muscle may be easily expanded under in vitro conditions. The most frequently used medium is Dulbecco's modified Eagle medium (D-MEM) supplemented with fetal bovine serum and/or horse serum in varying concentrations [34,59]. Several authors supplemented their media with chick embryo extract or various growth factors (e.g.…”

“…Several authors demonstrated the potential of stem cells derived from skeletal muscles to differentiate into cardiomyocytes [41,76]. Okada et al [59] injected populations of myogenic endothelial cells into immune-deficient mice with induced acute myocardial infarction. They observed improvement in left ventricular function six weeks after administration.…”

“…They observed improvement in left ventricular function six weeks after administration. Moreover, transplanted cells generated robust engraftments within the infarcted myocardium, and also stimulated angiogenesis, attenuation of scar tissue, and proliferation and survival of endogenous cardiomyocytes [59]. More recently, Shibuya and coworkers transplanted stem cells isolated from tongue muscle into a mouse model of myocardial infarction.…”