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

SUBMITTER: Di Maggio N 

PROVIDER: S-EPMC5349595 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Extracellular matrix and α<sub>5</sub>β<sub>1</sub> integrin signaling control the maintenance of bone formation capacity by human adipose-derived stromal cells.

Di Maggio Nunzia N   Martella Elisa E   Frismantiene Agne A   Resink Therese J TJ   Schreiner Simone S   Lucarelli Enrico E   Jaquiery Claude C   Schaefer Dirk J DJ   Martin Ivan I   Scherberich Arnaud A  

Scientific reports 20170314


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  ...[more]

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