Sphingosine 1-phosphate receptor 1 is required for MMP-2 function in bone marrow mesenchymal stromal cells: implications for cytoskeleton assembly and proliferation

Bone marrow-derived mesenchymal stromal cell- (BM-MSC-) based therapy is a promising option for regenerative medicine. An important role in the control of the processes influencing the BM-MSC therapeutic efficacy, namely, extracellular matrix remodelling and proliferation and secretion ability, is played by matrix metalloproteinase- (MMP-) 2. Therefore, the identification of paracrine/autocrine regulators of MMP-2 function may be of great relevance for improving BM-MSC therapeutic potential. We recently reported that BM-MSCs release the bioactive lipid sphingosine 1-phosphate (S1P) and, here, we demonstrated an impairment of MMP-2 expression/release when the S1P receptor subtype S1PR1 is blocked. Notably, active S1PR1/MMP-2 signalling is required for F-actin structure assembly (lamellipodia, microspikes, and stress fibers) and, in turn, cell proliferation. Moreover, in experimental conditions resembling the damaged/regenerating tissue microenvironment (hypoxia), S1P/S1PR1 system is also required for HIF-1α expression and vinculin reduction. Our findings demonstrate for the first time the trophic role of S1P/S1PR1 signalling in maintaining BM-MSCs' ability to modulate MMP-2 function, necessary for cytoskeleton reorganization and cell proliferation in both normoxia and hypoxia. Altogether, these data provide new perspectives for considering S1P/S1PR1 signalling a pharmacological target to preserve BM-MSC properties and to potentiate their beneficial potential in tissue repair

L\u2019Aquila, 6 aprile 2009: la gestione dell\u2019emergenza, la promozione della coesione e della salute sociale

Il presente lavoro nasce nell\u2019ambito del Progetto Vela, che si pone come obiettivo generale "la promozione della salute\u201d in comunit\ue0 colpite da emergenza sia naturale che umanitaria. Il Progetto \ue8 un\u2019iniziativa elaborata da un gruppo di ricercato- ri afferenti all\u2019Universit\ue0 degli Studi di Padova (dipartimento FISPPA \u2013 Filosofia, Sociologia, Pedagogia e Psicologia Applicata), nato nell\u2019ottobre 2011 con l\u2019obietti- vo di indagare quali siano state le ricadute negli assetti interattivi della comunit\ue0 aquilana, ossia come essa configuri la propria realt\ue0 sociale, in seguito al sisma del 6 aprile 2009. L\u2019incipit dell\u2019articolo consiste in una riflessione teorico-conoscitiva sulla relazione tra \u201ccatastrofe\u201d, \u201csalute\u201d ed \u201cemergenza\u201d, che ha porta-to ad assumere la rilevanza di indagarli per come sono configurati dai membri della comunit\ue0, anzich\ue9 considerarli entit\ue0 statiche di per s\ue9. Coerentemente con questi assunti, attraverso appositi protocolli di indagine, sono state indagate le modalit\ue0 discorsive che configurano la "salute" del territorio aquilano prima del sisma, nelle ore di urgenza del post-sisma, allo stato attuale e in proiezione futura. I protocolli sono stati somministrati a diversi ruoli (cittadini, commercianti, insegnanti, forze dell\u2019ordine, operatori della protezione civile, medici e psicologi), in modo da raccogliere il testo di tutte le voci della comunit\ue0 aquilana. Quanto emerso ha mostrato che gli aquilani tuttora configurano la loro comunit\ue0 come "catastrofica" e dunque associata all\u2019evento sismico; dunque quest\u2019ultimo ha pervaso, e pervade, la biografia della comunit\ue0 aquilana (sia in prospettiva passata, che presente, che futura) con alto tasso di potenziale disgregazione sociale

Mesenchymal Stromal Cell Secreted Sphingosine 1-Phosphate (S1P) Exerts a Stimulatory Effect on Skeletal Myoblast Proliferation.

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

Platelet rich plasma (PRP): new perspectives in skeletal muscle regeneration after damage

Adult skeletal muscle can undergo regeneration after damage, thanks to a resident population of stem cells, namely satellite cells, located underneath the basement membrane of the skeletal muscle fibers. However, these cells are scarce in number and, in case of severe and extended muscle damage, they cannot be efficient enough as to promote tissue repair. Recent trends in the field of regenerative medicine are attempting to identify novel strategies aimed to improve the endogenous tissue repair potential and contribute to the recreation of a less hostile microenvironment for muscle cell progenitors functionality. In such perspective, platelet rich plasma (PRP) appears to be provided with several desirable properties for regenerative purposes, representing a source of multiple growth factors, as well as an optimal substitute for animal serum [1-3]. On these bases, in this study we evaluated the effect of PRP on C2C12 myoblasts in terms of viability, proliferation and myogenic differentiative potential. It was found that PRP, used at different concentrations, was able to positively influence C2C12 cell viability and proliferation as observed by MTS assay, EdU incorporation and confocal immunofluorescence analysis of Ki67 expression. The differentiative potential of C2C12 myoblasts treated with PRP was investigated by confocal immunofluorescence analysis of the expression of specific markers. In conclusion, our preliminary data suggest that PRP may play a pivotal role in skeletal muscle regeneration and can be considered as a valuable tool in designing therapeutic protocols in the field of regenerative medicine

Platelet rich plasma (PRP): new perspectives in skeletal muscle regeneration after damage

Adult skeletal muscle can undergo regeneration after damage, thanks to a resident population of stem cells, namely satellite cells, located underneath the basement membrane of the skeletal muscle fibers. However, these cells are scarce in number and, in case of severe and extended muscle damage, they cannot be efficient enough as to promote tissue repair. Recent trends in the field of regenerative medicine are attempting to identify novel strategies aimed to improve the endogenous tissue repair potential and contribute to the recreation of a less hostile microenvironment for muscle cell progenitors functionality. In such perspective, platelet rich plasma (PRP) appears to be provided with several desirable properties for regenerative purposes, representing a source of multiple growth factors, as well as an optimal substitute for animal serum [1-3]. On these bases, in this study we evaluated the effect of PRP on C2C12 myoblasts in terms of viability, proliferation and myogenic differentiative potential. It was found that PRP, used at different concentrations, was able to positively influence C2C12 cell viability and proliferation as observed by MTS assay, EdU incorporation and confocal immunofluorescence analysis of Ki67 expression. The differentiative potential of C2C12 myoblasts treated with PRP was investigated by confocal immunofluorescence analysis of the expression of specific markers. In conclusion, our preliminary data suggest that PRP may play a pivotal role in skeletal muscle regeneration and can be considered as a valuable tool in designing therapeutic protocols in the field of regenerative medicine

Modulation of MMP-2 function in bone marrow mesenchymal stromal cells requires sphingosine 1-phopsphate receptor 1 mediated signaling: implications for cytoskeletal assembly and proliferation

Bone-marrow-derived mesenchymal stromal cells (BM-MSCs)–based therapy represents a promising option in the field of regenerative medicine. Their therapeutic potential is mainly dependent on paracrine secretion, proliferation and ECM remodeling abilities whose modulation involves Matrix Metalloproteinase (MMP)-2 functionality. Thus, the identification of paracrine/autocrine factors regulating MMP-2 expression/activity may be of great biological relevance for potentiating BM-MSC theraputic efficacy. Our research group has demonstrated that BM-MSCs release the bioactive lipid sphingosine-1-phosphate (S1P). Here we demonstrated : i) the requirement for BM-MSC of S1P production to synthesize functional gelatinases; ii) an impairment of gelatinolytic activity and MMP-2 expression/release when the S1P receptor subtype 1 (S1PR1) is blocked. Notably, in these experimental conditions BM-MSCs did not exhibit the formation of plasmamembrane-associated F-actin structures (lamellipodia, filopodia, microspikes) and, in turn, showed a reduction of the proliferation rate. Moreover, S1P1-mediated signaling is required for HIF-1alpha expression and MMP-2 expression/activity, reduction of vinculin expression and stress fiber formation and proliferation in hypoxia, an experimental condition mimicking the injured/regenerating tissue microenvironment. In conclusion, our findings, demonstrating the trophic role exerted by the autocrine S1P/S1PR1 signaling in maintaining BM-MSC ability to modulate MMP-2 function, required for ECM remodeling, cytoskeleton assembly and cell proliferation may provide perspectives for considering S1P/S1PR1 as a pharmacological target to preserve BM-MSCs properties and improve their efficacy in tissue repair

Dal collezionismo privato alle istituzioni pubbliche

Il progetto, nato all\u2019interno di corso di Museologia e collezionismo della Scuola di Specializzazione in Beni storico-artistici \u2013 DAR, riguarda la schedatura di opere conservate in istituzioni molto diverse l'una dall'altra e costituiscono una testimonianza della variet\ue0 di approcci e di fonti relative alla storia del collezionismo. Con introduzione di M. Pigozzi e schede di A. Barbanti, G. Cali, I. Carozza, I. Chia, L. Coppa, A. Di Maio, Cristina Elia, C. Forconi, F. Gamba, A. Lisbona, M. Mariano, S. Mauro, F. Passerini, L. Regano, G.M. Sassoli de\u2019 Bianchi Strozzi, I. Siboni, S. Zugni