Neighboring cells override 3D hydrogel matrix cues to drive human MSC quiescence.

Biomaterials
Silvia A FerreiraEileen Gentleman

Abstract

Physical properties of modifiable hydrogels can be tuned to direct stem cell differentiation in a role akin to that played by the extracellular matrix in native stem cell niches. However, stem cells do not respond to matrix cues in isolation, but rather integrate soluble and non-soluble signals to balance quiescence, self-renewal and differentiation. Here, we encapsulated single cell suspensions of human mesenchymal stem cells (hMSC) in hyaluronic acid-based hydrogels at high and low densities to unravel the contributions of matrix- and non-matrix-mediated cues in directing stem cell response. We show that in high-density (HD) cultures, hMSC do not rely on hydrogel cues to guide their fate. Instead, they take on characteristics of quiescent cells and secrete a glycoprotein-rich pericellular matrix (PCM) in response to signaling from neighboring cells. Preventing quiescence precluded the formation of a glycoprotein-rich PCM and forced HD cultures to differentiate in response to hydrogel composition. Our observations may have important implications for tissue engineering as neighboring cells may act counter to matrix cues provided by scaffolds. Moreover, as stem cells are most regenerative if activated from a quiescent state, our...Continue Reading

Citations

Feb 28, 2020·Advanced Healthcare Materials·Rebecca A ScottRobert E Akins
Jan 17, 2020·Advanced Healthcare Materials·Christoph SalzlechnerEileen Gentleman
Jan 25, 2020·Nature Biomedical Engineering·Ulrich BlacheEileen Gentleman
Apr 11, 2020·Tissue Engineering. Part B, Reviews·Jianrui Ma, Chengyang Huang
Oct 6, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Nicky W TamJohn P Frampton
Oct 7, 2020·Proceedings of the National Academy of Sciences of the United States of America·Joshua M GrolmanDavid J Mooney
Oct 18, 2020·Journal of Biomechanical Engineering·Rukmani SridharanFergal J O'Brien
Mar 3, 2021·Acta Biomaterialia·Suzette T LustEileen Gentleman
May 6, 2021·Materials Science & Engineering. C, Materials for Biological Applications·Mariane B SordiPaul T Sharpe
Jun 22, 2021·ACS Biomaterials Science & Engineering·Suzette T LustEileen Gentleman
Jul 3, 2021·Advanced Functional Materials·Claudia LoebelJason A Burdick
Oct 14, 2019·ACS Biomaterials Science & Engineering·Taimoor H QaziSven Geissler

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Methods Mentioned

BETA
flow cytometry
PCR
fluorescence imaging
acetylation

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GraphPad
Excel
Elements Advanced Research Analysis
GraphPad Prism
NIS
Perseus
MaxQuant
Andromeda
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