Extracellular matrix and α5β1 integrin signaling control the maintenance of bone formation capacity by human adipose-derived stromal cells

• Published in: Scientific reports Vol. 7; no. 1; p. 44398
• Main Authors: Di Maggio, Nunzia, Martella, Elisa, Frismantiene, Agne, Resink, Therese J., Schreiner, Simone, Lucarelli, Enrico, Jaquiery, Claude, Schaefer, Dirk J., Martin, Ivan, Scherberich, Arnaud
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.03.2017; Nature Publishing Group
• Subjects: 13/100; 13/51; 13/95; 14; 14/19; 631/532/2118/2074; 631/532/2139; 64/60; 96/106; 96/31; 96/63; Humanities and Social Sciences; multidisciplinary; Science
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep44398

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 α 5 integrin (CD49e), which was instead upregulated in P0- and Pass-ASC. Mechanistically, induced activation of α 5 β 1 integrin in Unpass-ASC led to a significant loss of bone formation in vivo . This study shows that ECM and regulation of α 5 β 1 -integrin signaling preserve ASC progenitor properties, including bone tissue-forming capacity, during in vitro expansion.