A role for matrix stiffness in the regulation of cardiac side population cell function.
The mechanical properties of the local microenvironment may have important influence on the fate and function of adult tissue progenitor cells, altering the regenerative process. This is particularly critical following a myocardial infarction, in which the normal, compliant myocardial tissue is replaced with fibrotic, stiff scar tissue. In this study, we examined the effects of matrix stiffness on adult cardiac side population (CSP) progenitor cell behavior. Ovine and murine CSP cells were isolated and cultured on polydimethylsiloxane substrates, replicating the elastic moduli of normal and fibrotic myocardium. Proliferation capacity and cell cycling were increased in CSP cells cultured on the stiff substrate with an associated reduction in cardiomyogeneic differentiation and accelerated cell ageing. In addition, culture on stiff substrate stimulated upregulation of extracellular matrix and adhesion proteins gene expression in CSP cells. Collectively, we demonstrate that microenvironment properties, including matrix stiffness, play a critical role in regulating progenitor cell functions of endogenous resident CSP cells. Understanding the effects of the tissue microenvironment on resident cardiac progenitor cells is a critical step toward achieving functional cardiac regeneration.
Divisions of Genetics and Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts;
Yiling
Y
Qiu
Divisions of Genetics and Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Orthopedics and Sports Medicine, School of Medicine, University of Washington, Seattle, Washington; and.
Ahmad F
AF
Bayomy
Divisions of Genetics and Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts;
Marcus V
MV
Gomez
Divisions of Genetics and Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts;
Michael
M
Bauer
Department of Mechanical Engineering, Boston University, Boston, Massachusetts.
Ping
P
Du
Divisions of Genetics and Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts;
Yanfei
Y
Yang
Department of Mechanical Engineering, Boston University, Boston, Massachusetts.
Xin
X
Zhang
Divisions of Genetics and Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; rliao@rics.bwh.harvard.edu.
Ronglih
R
Liao
D053687:Adult Stem Cells / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002448:Cell Adhesion; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence; D018920:Coculture Techniques; D004129:Dimethylpolysiloxanes / Q000737:chemistry*; D055119:Elastic Modulus; D008297:Male; D040542:Mechanotransduction, Cellular; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology*; D010641:Phenotype; D012756:Sheep; D058985:Side-Population Cells / Q000378:metabolism / Q000502:physiology*; D055153:Stem Cell Niche; D013997:Time Factors
D004129:Dimethylpolysiloxanes; C013830:baysilon
cardiac side population cell; cell cycle regulation; cellular ageing; differentiation; matrix stiffness; proliferation