title: Mechanical loading of stem cells for improvement of transplantation outcome in a model of acute myocardial infarction: the role of loading history.
abstract: Stem cell therapy for tissue repair is a rapidly evolving field and the factors that dictate the physiological responsiveness of stem cells remain under intense investigation. In this study we hypothesized that the mechanical loading history of muscle-derived stem cells (MDSCs) would significantly impact MDSC survival, host tissue angiogenesis, and myocardial function after MDSC transplantation into acutely infarcted myocardium. Mice with acute myocardial infarction by permanent left coronary artery ligation were injected with either nonstimulated (NS) or mechanically stimulated (MS) MDSCs. Mechanical stimulation consisted of stretching the cells with equibiaxial stretch with a magnitude of 10% and frequency of 0.5 Hz. MS cell-transplanted hearts showed improved cardiac contractility, increased numbers of host CD31+ cells, and decreased fibrosis, in the peri-infarct region, compared to the hearts treated with NS MDSCs. MS MDSCs displayed higher vascular endothelial growth factor expression than NS cells in vitro. These findings highlight an important role for cyclic mechanical loading preconditioning of donor MDSCs in optimizing MDSC transplantation for myocardial repair.
authors.affiliation: Department of Orthopaedic Surgery, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Theresa R
authors.initials: TR
authors.lastname: Cassino
authors.forename: Lauren
authors.initials: L
authors.lastname: Drowley
authors.forename: Masaho
authors.initials: M
authors.lastname: Okada
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Beckman
authors.forename: Bradley
authors.initials: B
authors.lastname: Keller
authors.forename: Kimimasa
authors.initials: K
authors.lastname: Tobita
authors.forename: Philip R
authors.initials: PR
authors.lastname: Leduc
authors.forename: Johnny
authors.initials: J
authors.lastname: Huard
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002921:Cicatrix / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D006334:Heart Function Tests; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D018919:Neovascularization, Physiologic; D018384:Oxidative Stress; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D013314:Stress, Mechanical; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A