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

Nunzia Di Maggio, Elisa Martella, Agne Frismantiene, Therese J. Resink, Simone Schreiner, Enrico Lucarelli, Claude Jaquiery, Dirk Johannes Schaefer, Ivan Martin, Arnaud Scherberich

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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 α5 integrin (CD49e), which was instead upregulated in P0- and Pass-ASC. Mechanistically, induced activation of α5β1 integrin 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.
Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - Mar 14 2017

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Stromal Cells
Osteogenesis
Integrins
Extracellular Matrix
Stem Cells
Maintenance
Blood Vessels
Bone and Bones
Integrin alpha5beta1
Fibronectins
Adipose Tissue
Transplants

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Extracellular matrix and α5β1 integrin signaling control the maintenance of bone formation capacity by human adipose-derived stromal cells. / Di Maggio, Nunzia; Martella, Elisa; Frismantiene, Agne; Resink, Therese J.; Schreiner, Simone; Lucarelli, Enrico; Jaquiery, Claude; Schaefer, Dirk Johannes; Martin, Ivan; Scherberich, Arnaud.

In: Scientific Reports, Vol. 7, 14.03.2017, p. 1-12.

Research output: Contribution to journalArticle

Di Maggio, N, Martella, E, Frismantiene, A, Resink, TJ, Schreiner, S, Lucarelli, E, Jaquiery, C, Schaefer, DJ, Martin, I & Scherberich, A 2017, 'Extracellular matrix and α5β1 integrin signaling control the maintenance of bone formation capacity by human adipose-derived stromal cells.', Scientific Reports, vol. 7, pp. 1-12. https://doi.org/10.1038/srep44398
Di Maggio, Nunzia ; Martella, Elisa ; Frismantiene, Agne ; Resink, Therese J. ; Schreiner, Simone ; Lucarelli, Enrico ; Jaquiery, Claude ; Schaefer, Dirk Johannes ; Martin, Ivan ; Scherberich, Arnaud. / Extracellular matrix and α5β1 integrin signaling control the maintenance of bone formation capacity by human adipose-derived stromal cells. In: Scientific Reports. 2017 ; Vol. 7. pp. 1-12.
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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 α5 integrin (CD49e), which was instead upregulated in P0- and Pass-ASC. Mechanistically, induced activation of α5β1 integrin 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.",
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