Mechanical Loading of Stem Cells for Improvement of Transplantation Outcome in a Model of Acute Myocardial Infarction: The Role of Loading History

• Published in: Tissue engineering. Part A Vol. 18; no. 11-12; pp. 111 - 1108
• Main Authors: Cassino, Theresa R., Drowley, Lauren, Okada, Masaho, Beckman, Sarah A., Keller, Bradley, Tobita, Kimimasa, LeDuc, Philip R., Huard, Johnny
• Format: Journal Article
• Language: English
• Published: United States Mary Ann Liebert, Inc 01.06.2012
• Subjects: Angiogenesis; Animal models; Animals; Biomechanical Phenomena; Cell Differentiation; Cell Proliferation; Cell Survival; Cicatrix - pathology; Cicatrix - physiopathology; coronary artery; Disease Models, Animal; Donors; Fibrosis; Heart; Heart attacks; Heart Function Tests; Ischemic Preconditioning, Myocardial; Male; Mechanical loading; Mechanical stimuli; Mice; Mice, Inbred C57BL; Muscle contraction; Myocardial infarction; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Myocardial Infarction - therapy; Myocardium; Myocardium - pathology; Neovascularization, Physiologic; Original; Original Articles; Oxidative Stress; Stem Cell Transplantation; Stem cells; Stem Cells - cytology; Stress, Mechanical; Tissue engineering; Transplants & implants; Treatment Outcome; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 1937-3341; 1937-335X
• DOI: 10.1089/ten.tea.2011.0285

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.