title: Mesenchymal stromal cell secreted sphingosine 1-phosphate (S1P) exerts a stimulatory effect on skeletal myoblast proliferation.
abstract: Bone-marrow-derived mesenchymal stromal cells (MSCs) have the potential to significantly contribute to skeletal muscle healing through the secretion of paracrine factors that support proliferation and enhance participation of the endogenous muscle stem cells in the process of repair/regeneration. However, MSC-derived trophic molecules have been poorly characterized. The aim of this study was to investigate paracrine signaling effects of MSCs on skeletal myoblasts. It was found, using a biochemical and morphological approach that sphingosine 1-phosphate (S1P), a natural bioactive lipid exerting a broad range of muscle cell responses, is secreted by MSCs and represents an important factor by which these cells exert their stimulatory effects on C2C12 myoblast and satellite cell proliferation. Indeed, exposure to conditioned medium obtained from MSCs cultured in the presence of the selective sphingosine kinase inhibitor (iSK), blocked increased cell proliferation caused by the conditioned medium from untreated MSCs, and the addition of exogenous S1P in the conditioned medium from MSCs pre-treated with iSK further increased myoblast proliferation. Finally, we also demonstrated that the myoblast response to MSC-secreted vascular endothelial growth factor (VEGF) involves the release of S1P from C2C12 cells. Our data may have important implications in the optimization of cell-based strategies to promote skeletal muscle regeneration.
authors.affiliation: Department of Experimental and Clinical Medicine - Section of Anatomy and Histology, University of Florence, Florence, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Sassoli
authors.affiliation: Department of Biomedical, Experimental and Clinical Sciences "Mario Serio" - Unit of Biochemical Sciences and Molecular Biology, University of Florence, Florence, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Frati
authors.affiliation: Department of Experimental and Clinical Medicine - Section of Anatomy and Histology, University of Florence, Florence, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Tani
authors.affiliation: Department of Biomedical, Experimental and Clinical Sciences "Mario Serio" - Unit of Biochemical Sciences and Molecular Biology, University of Florence, Florence, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Anderloni
authors.affiliation: Department of Biomedical, Experimental and Clinical Sciences "Mario Serio" - Unit of Biochemical Sciences and Molecular Biology, University of Florence, Florence, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Pierucci
authors.affiliation: Department of Biomedical, Experimental and Clinical Sciences "Mario Serio" - Unit of Biochemical Sciences and Molecular Biology, University of Florence, Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Matteini
authors.affiliation: Department of Experimental and Clinical Medicine - Section of Anatomy and Histology, University of Florence, Florence, Italy.
authors.forename: Flaminia
authors.initials: F
authors.lastname: Chellini
authors.affiliation: Department of Experimental and Clinical Medicine - Section of Anatomy and Histology, University of Florence, Florence, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Zecchi Orlandini
authors.affiliation: Department of Experimental and Clinical Medicine - Section of Anatomy and Histology, University of Florence, Florence, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Formigli
authors.affiliation: Department of Biomedical, Experimental and Clinical Sciences "Mario Serio" - Unit of Biochemical Sciences and Molecular Biology, University of Florence, Florence, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Meacci
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D008246:Lysophospholipids / Q000378:metabolism / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D032448:Myoblasts, Skeletal / Q000378:metabolism*; D019899:Paracrine Communication / Q000187:drug effects; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors; D012038:Regeneration / Q000187:drug effects*; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects; D000099157:Sphingosine Kinase
chemical_list: D017077:Culture Media, Conditioned; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D013110:Sphingosine; D042461:Vascular Endothelial Growth Factor A; D000099157:Sphingosine Kinase; C467480:vascular endothelial growth factor A, mouse; C060506:sphingosine 1-phosphate