title: Mechanical loading modulates the differentiation state of vascular smooth muscle cells.
abstract: The cause underlying the onset of stenosis after vascular reconstruction is not well understood. In the present study, we evaluated the effect of mechanical unloading on the differentiation state of human vascular smooth muscle cells (hVSMCs) using a tissue-engineered vascular media (TEVM). hVSMCs cultured in a mechanically loaded three-dimensional environment, known as a living tissue sheet, had a higher differentiated state than cells grown on plastic. When the living tissue sheet was detached from its support, the release of the residual stress resulted in a mechanical unloading and cells within the extracellular matrix (ECM) dedifferentiated as shown by downregulation of differentiation markers. The relaxed living tissue sheet can be rolled onto a tubular mandrel to form a TEVM. The rolling procedure resulted in the reintroduction of a mechanical load leading to a cohesive compacted tissue. During this period, cells gradually redifferentiated and aligned circumferentially to the tubular support. Our results suggest that differentiation of hVSMCs can be driven by mechanical loading and may occur simultaneously in the absence of other cell types. The extrapolation of our results to the clinical context suggests the hypothesis that hVSMCs may adopt a proliferative phenotype resulting from the mechanical unloading of explanted blood vessels during vascular reconstruction. Therefore, we propose that this mechanical unloading may play an important role in the onset of vascular graft stenosis.
authors.affiliation: Laboratoire d'Organogénèse Expérimentale (LOEX), Hôpital du Saint-Sacrement du CHA, 1050, chemin Sainte-Foy, Québec, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Grenier
authors.forename: Murielle
authors.initials: M
authors.lastname: Rémy-Zolghadri
authors.forename: François
authors.initials: F
authors.lastname: Bergeron
authors.forename: Rina
authors.initials: R
authors.lastname: Guignard
authors.forename: Kathleen
authors.initials: K
authors.lastname: Baker
authors.forename: Raymond
authors.initials: R
authors.lastname: Labbé
authors.forename: François A
authors.initials: FA
authors.lastname: Auger
authors.forename: Lucie
authors.initials: L
authors.lastname: Germain
mesh_terms: D002452:Cell Count; D002454:Cell Differentiation; D002455:Cell Division; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003251:Constriction, Pathologic / Q000209:etiology; D003470:Culture Media; D005109:Extracellular Matrix / Q000378:metabolism; D005434:Flow Cytometry; D005562:Formazans / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007202:Indicators and Reagents / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000502:physiology*; D009499:Neutral Red / Q000494:pharmacology; D009924:Organ Culture Techniques; D013314:Stress, Mechanical; D013778:Tetrazolium Salts / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods*; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D003470:Culture Media; D005562:Formazans; D007202:Indicators and Reagents; D013778:Tetrazolium Salts; C079782:MTT formazan; D009499:Neutral Red