Myogenic endothelial cells purified from human skeletal muscle improve cardiac function after transplantation into infarcted myocardium.
OBJECTIVE
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.
Okada
Masaho
M
Stem Cell Research Center, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania; Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Payne
Thomas R
TR
Stem Cell Research Center, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania; Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Bioengineering, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Zheng
Bo
B
Stem Cell Research Center, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania; Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Oshima
Hideki
H
Stem Cell Research Center, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania; Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Momoi
Nobuo
N
Department of Pediatrics, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.
Tobita
Kimimasa
K
Department of Pediatrics, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania; Department of Bioengineering, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Keller
Bradley B
BB
Department of Pediatrics, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.
Phillippi
Julie A
JA
Stem Cell Research Center, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania; Carnegie Mellon University, Pittsburgh, Pennsylvania.
Péault
Bruno
B
Stem Cell Research Center, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania; Department of Pediatrics, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.
Huard
Johnny
J
Stem Cell Research Center, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania; Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Bioengineering, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Electronic address: jhuard@pitt.edu.
D000328:Adult; D000818:Animals; D017209:Apoptosis; D002469:Cell Separation; D017690:Cell Transplantation / Q000379:methods*; D042783:Endothelial Cells / Q000166:cytology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D032446:Myoblasts / Q000166:cytology; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A