title: Extracellular matrix and α5β1integrin signaling control the maintenance of bone formation capacity by human adipose-derived stromal cells.
abstract: Stromal vascular fraction (SVF) cells of human adipose tissue have the capacity to generate osteogenic grafts with intrinsic vasculogenic properties. However, adipose-derived stromal/stem cells (ASC), even after minimal monolayer expansion, display poor osteogenic capacity in vivo. We investigated whether ASC bone-forming capacity may be maintained by culture within a self-produced extracellular matrix (ECM) that recapitulates the native environment. SVF cells expanded without passaging up to 28 days (Unpass-ASC) deposited a fibronectin-rich extracellular matrix and displayed greater clonogenicity and differentiation potential in vitro compared to ASC expanded only for 6 days (P0-ASC) or for 28 days with regular passaging (Pass-ASC). When implanted subcutaneously, Unpass-ASC produced bone tissue similarly to SVF cells, in contrast to P0- and Pass-ASC, which mainly formed fibrous tissue. Interestingly, clonogenic progenitors from native SVF and Unpass-ASC expressed low levels of the fibronectin receptor α5integrin (CD49e), which was instead upregulated in P0- and Pass-ASC. Mechanistically, induced activation of α5β1integrin in Unpass-ASC led to a significant loss of bone formation in vivo. This study shows that ECM and regulation of α5β1-integrin signaling preserve ASC progenitor properties, including bone tissue-forming capacity, during in vitro expansion.
authors.affiliation: Laboratory of Tissue Engineering, Department of Surgery, University Hospital of Basel and Department of Biomedicine, University of Basel, Switzerland.
authors.forename: Nunzia
authors.initials: N
authors.lastname: Di Maggio
authors.affiliation: Osteoarticular Regeneration Laboratory, Istituto Ortopedico Rizzoli, Bologna, Italy.|Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Martella
authors.affiliation: Laboratory of Signal Transduction, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Agne
authors.initials: A
authors.lastname: Frismantiene
authors.affiliation: Laboratory of Signal Transduction, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Therese J
authors.initials: TJ
authors.lastname: Resink
authors.affiliation: Laboratory of Tissue Engineering, Department of Surgery, University Hospital of Basel and Department of Biomedicine, University of Basel, Switzerland.
authors.forename: Simone
authors.initials: S
authors.lastname: Schreiner
authors.affiliation: Osteoarticular Regeneration Laboratory, Istituto Ortopedico Rizzoli, Bologna, Italy.|Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Lucarelli
authors.affiliation: Clinic for Oral and Maxillofacial Surgery, University Hospital of Basel, Basel, Switzerland.
authors.forename: Claude
authors.initials: C
authors.lastname: Jaquiery
authors.affiliation: Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital of Basel, Switzerland.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Schaefer
authors.affiliation: Laboratory of Tissue Engineering, Department of Surgery, University Hospital of Basel and Department of Biomedicine, University of Basel, Switzerland.
authors.forename: Ivan
authors.initials: I
authors.lastname: Martin
authors.affiliation: Laboratory of Tissue Engineering, Department of Surgery, University Hospital of Basel and Department of Biomedicine, University of Basel, Switzerland.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Scherberich
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D001846:Bone Development / Q000235:genetics; D001842:Bone and Bones / Q000166:cytology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000235:genetics*; D005109:Extracellular Matrix / Q000235:genetics; D005353:Fibronectins / Q000235:genetics; D006801:Humans; D039081:Integrin alpha5beta1 / Q000235:genetics*; D051379:Mice; D010012:Osteogenesis / Q000235:genetics*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D017154:Stromal Cells / Q000166:cytology*
chemical_list: D005353:Fibronectins; D039081:Integrin alpha5beta1