title: Mechanical characterization of human mesenchymal stem cells subjected to cyclic uniaxial strain and TGF-β1.
abstract: Human mesenchymal stem cells (hMSCs) have shown promising potential in the field of regenerative medicine particularly in vascular tissue engineering. Optimal growing of MSCs into specific lineage requires a thorough understanding of the role of mechanobiology in MSC metabolism. Although effects of external physical cues (mechanical stimuli through external loading and scaffold properties) on regulation of MSC differentiation into Smooth muscle (SM) lineage have attracted widespread attention, fewer studies are available on mechanical characterization of single engineered MSCs which is vital in tissue development through proper mechanotransductive cell-environment interactions. In this study, we investigated effects of uniaxial tensile strain and transforming growth factor-β1 (TGF-β1) stimulations on mechanical properties of engineered MSCs and their F-actin cytoskeleton organization. Micropipette aspiration technique was used to measure mechanical properties of MSCs including mean Young׳s modulus (E) and the parameters of standard linear viscoelastic model. Compared to control samples, MSCs treated by uniaxial strain either with or without TGF-β1 indicated significant increases in E value and considerable drop in creep compliance curve, while samples treated by TGF-β1 alone met significant decreases in E value and considerable rise in creep compliance curve. Among treated samples, uniaxial tensile strain accompanied by TGF-β1 stimulation not only caused higher stimulation in MSC differentiation towards SM phenotype at transcriptional level, but also created more structural integrity in MSCs due to formation of thick bundled F-actin fibers. Results can be applied in engineering of MSCs towards functional target cells and consequently tissue development.
authors.affiliation: Department of Tissue Engineering, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad-Mehdi
authors.initials: MM
authors.lastname: Khani
authors.affiliation: Cardiovascular Engineering Lab, Faculty of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran. Electronic address: tafazoli@aut.ac.ir.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Tafazzoli-Shadpour
authors.affiliation: Cardiovascular Engineering Lab, Faculty of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Goli-Malekabadi
authors.affiliation: National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Nooshin
authors.initials: N
authors.lastname: Haghighipour
mesh_terms: D001696:Biomechanical Phenomena / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D060846:Cell Engineering; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects; D013314:Stress, Mechanical; D059467:Transcriptome / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D053773:Transforming Growth Factor beta1
keywords: Cell viscoelasticity; Differentiation; Functional tissue engineering; Micropipette aspiration; Uniaxial strain