title: Muscle acellular scaffold as a biomaterial: effects on C2C12 cell differentiation and interaction with the murine host environment.
abstract: The extracellular matrix (ECM) of decellularized organs possesses the characteristics of the ideal tissue-engineering scaffold (i.e., histocompatibility, porosity, degradability, non-toxicity). We previously observed that the muscle acellular scaffold (MAS) is a pro-myogenic environment in vivo. In order to determine whether MAS, which is basically muscle ECM, behaves as a myogenic environment, regardless of its location, we analyzed MAS interaction with both muscle and non-muscle cells and tissues, to assess the effects of MAS on cell differentiation. Bone morphogenetic protein treatment of C2C12 cells cultured within MAS induced osteogenic differentiation in vitro, thus suggesting that MAS does not irreversibly commit cells to myogenesis. In vivo MAS supported formation of nascent muscle fibers when replacing a muscle (orthotopic position). However, heterotopically grafted MAS did not give rise to muscle fibers when transplanted within the renal capsule. Also, no muscle formation was observed when MAS was transplanted under the xiphoid process, in spite of the abundant presence of cells migrating along the laminin-based MAS structure. Taken together, our results suggest that MAS itself is not sufficient to induce myogenic differentiation. It is likely that the pro-myogenic environment of MAS is not strictly related to the intrinsic properties of the muscle scaffold (e.g., specific muscle ECM proteins). Indeed, it is more likely that myogenic stem cells colonizing MAS recognize a muscle environment that ultimately allows terminal myogenic differentiation. In conclusion, MAS may represent a suitable environment for muscle and non-muscle 3D constructs characterized by a highly organized structure whose relative stability promotes integration with the surrounding tissues. Our work highlights the plasticity of MAS, suggesting that it may be possible to consider MAS for a wider range of tissue engineering applications than the mere replacement of volumetric muscle loss.
authors.affiliation: Department of Biological Adaptation and Aging (B2A) UMR 8256 CNRS - ERL U1164 INSERM, Sorbonne Universités, UPMC University Paris 06 Paris, France ; Maxillofacial Unit, Calabrodental Clinic Crotone, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Perniconi
authors.affiliation: Department of Biological Adaptation and Aging (B2A) UMR 8256 CNRS - ERL U1164 INSERM, Sorbonne Universités, UPMC University Paris 06 Paris, France ; AHFOS Department - Section of Histology and Medical Embryology, Sapienza University of Rome Rome, Italy ; Interuniversitary Institute of Miology (IIM) Rome, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Coletti
authors.affiliation: Maxillofacial Unit, Calabrodental Clinic Crotone, Italy ; AHFOS Department - Section of Histology and Medical Embryology, Sapienza University of Rome Rome, Italy ; Interuniversitary Institute of Miology (IIM) Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Aulino
authors.affiliation: AHFOS Department - Section of Histology and Medical Embryology, Sapienza University of Rome Rome, Italy ; Interuniversitary Institute of Miology (IIM) Rome, Italy ; UTAPRAD-DIM, ENEA Frascati, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Costa
authors.affiliation: UTAPRAD-DIM, ENEA Frascati, Italy ; Tor Vergata University of Rome Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Aprile
authors.affiliation: JSGEM Department - Section of Taranto, University of Bari Taranto, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Santacroce
authors.affiliation: Maxillofacial Unit, Calabrodental Clinic Crotone, Italy.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Chiaravalloti
authors.affiliation: Unite d'Ingénierie et de Therapie Cellulaire, Etablissement Français du Sang Ile de France, Université Paris-Est Créteil Créteil, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Coquelin
authors.affiliation: Unite d'Ingénierie et de Therapie Cellulaire, Etablissement Français du Sang Ile de France, Université Paris-Est Créteil Créteil, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chevallier
authors.affiliation: UTAPRAD-DIM, ENEA Frascati, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Teodori
authors.affiliation: AHFOS Department - Section of Histology and Medical Embryology, Sapienza University of Rome Rome, Italy ; Interuniversitary Institute of Miology (IIM) Rome, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Adamo
authors.affiliation: Maxillofacial Unit, Calabrodental Clinic Crotone, Italy ; Regenerative Medicine Section, Tecnologica Research Institute Crotone, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Marrelli
authors.affiliation: Maxillofacial Unit, Calabrodental Clinic Crotone, Italy ; Regenerative Medicine Section, Tecnologica Research Institute Crotone, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Tatullo
keywords: extracellular matrix; myogenic differentiation; niche; osteogenic differentiation; regenerative medicine; tissue engineering