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

• Published in: Journal of the American College of Cardiology Vol. 52; no. 23; pp. 1869 - 1880
• Main Authors: Okada, Masaho, MD, Payne, Thomas R., PhD, Zheng, Bo, MD, Oshima, Hideki, MD, PhD, Momoi, Nobuo, MD, Tobita, Kimimasa, MD, Keller, Bradley B., MD, Phillippi, Julie A., PhD, Péault, Bruno, PhD, Huard, Johnny, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.12.2008; Elsevier Limited
• Subjects: Adult; Angiogenesis; Animals; Apoptosis; Attenuation; Biopsy; Cardiology; Cardiomyocytes; Cardiovascular; Cell cycle; Cell growth; Cell Separation; Cell Transplantation - methods; Echocardiography; Endothelial cells; Endothelial Cells - cytology; Engraftment; Female; Flow Cytometry; Fluorescence; Heart; Heart failure; Heart transplantation; human stem cells; Humans; Immunohistochemistry; Internal Medicine; Ischemia; Laboratories; Male; Medical research; Mice; Muscle, Skeletal - cytology; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscles; Musculoskeletal system; Myoblasts; Myoblasts - cytology; Myocardial infarction; Myocardial Infarction - pathology; Myocardial Infarction - therapy; Myocardium; Myocardium - pathology; paracrine factors; Penicillin; Population; Regeneration; Repair; Skeletal muscle; Stem cells; Transplantation; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; VEGF; Ventricle; United States > US; California; skeletal myoblast; cTnI; EDA; MDSC; PCNA; fskMyHC; nuclear LacZ; cardiac-specific isoforms of troponin I; myocardial infarction; fluorescence-activated cell sorting; fractional area change; LV; FACS; phosphate-buffered saline; end-diastolic area; DMEM; TUNEL; SkM; enzyme-linked immunoadsorbent assay; FBS; cTnT; qPCR; left ventricle/ventricular; skeletal muscle; MI; paracrine factors; quantitative real-time polymerase chain reaction; PBS; VEGF; human stem cells; nLacZ; FAC; muscle-derived stem cell; Dulbecco's modified Eagle's medium; proliferating cell nuclear antigen; fetal bovine serum; terminal dUPT nick end-labeling; vascular endothelial growth factor; fast skeletal myosin heavy chain; cardiac-specific isoforms of troponin T; ELISA
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2008.07.064

Objectives The aim of this study 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 coexpress 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 with that seen in 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.