title: Extracorporeal shock waves modulate myofibroblast differentiation of adipose-derived stem cells.
abstract: Mesenchymal stem cells are precursors of myofibroblasts, cells deeply involved in promoting tissue repair and regeneration. However, since myofibroblast persistence is associated with the development of tissue fibrosis, the use of tools that can modulate stem cell differentiation toward myofibroblasts is central. Extracorporeal shock waves are transient short-term acoustic pulses first employed to treat urinary stones. They are a leading choice in the treatment of several orthopedic diseases and, notably, they have been reported as an effective treatment for patients with fibrotic sequels from burn scars. Based on these considerations, the aim of this study is to define the role of shock waves in modulating the differentiation of human adipose-derived stem cells toward myofibroblasts. Shock waves inhibit the development of a myofibroblast phenotype; they down-regulate the expression of the myofibroblast marker alpha smooth muscle actin and the extracellular matrix protein type I collagen. Functionally, stem cells acquire a more fibroblast-like profile characterized by a low contractility and a high migratory ability. Shock wave treatment reduces the expression of integrin alpha 11, a major collagen receptor in fibroblastic cells, involved in myofibroblast differentiation. Mechanistically, the resistance of integrin alpha 11-overexpressing cells to shock waves in terms of alpha smooth muscle actin expression and cell migration and contraction suggests also a role of this integrin in the translation of shock wave signal into stem cell responses. In conclusion, this in vitro study shows that stem cell differentiation toward myofibroblasts can be controlled by shock waves and, consequently, sustains their use as a therapeutic approach in reducing the risk of skin and tissue fibrosis.
authors.affiliation: Department of Medical Sciences, University of Turin, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Rinella
authors.affiliation: Department of Medical Sciences, University of Turin, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Marano
authors.affiliation: Med & Sport 2000 Srl, Turin, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Berta
authors.affiliation: Department of Medical Sciences, University of Turin, Italy.
authors.forename: Ornella
authors.initials: O
authors.lastname: Bosco
authors.affiliation: Plastic Surgery Unit, University of Turin, Turin, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Fraccalvieri
authors.affiliation: Oncological Endocrinology, City of Health and Science Hospital, Turin, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Fortunati
authors.affiliation: Department of Medical Sciences, University of Turin, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Frairia
authors.affiliation: Department of Medical Sciences, University of Turin, Italy.
authors.forename: Maria Graziella
authors.initials: MG
authors.lastname: Catalano
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D002454:Cell Differentiation; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D005355:Fibrosis / Q000473:pathology*; D019220:High-Energy Shock Waves; D006801:Humans; D066298:In Vitro Techniques / Q000379:methods*; D008875:Middle Aged; D058628:Myofibroblasts / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*; D014945:Wound Healing / Q000502:physiology*