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Microwell Geometry Modulates Interleukin-6 Secretion in Human Mesenchymal Stem Cells

Published online by Cambridge University Press:  11 July 2017

Xun Xu ,
Weiwei Wang ,
Zhengdong Li ,
Karl Kratz ,
Nan Ma  and
Andreas Lendlein
Xun Xu
Affiliation:
Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany
Weiwei Wang
Affiliation:
Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany
Zhengdong Li
Affiliation:
Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany
Karl Kratz
Affiliation:
Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany Helmholtz Virtual Institute - Multifunctional Materials in Medicine, Berlin and Teltow, Teltow, Germany
Nan Ma
Affiliation:
Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany Helmholtz Virtual Institute - Multifunctional Materials in Medicine, Berlin and Teltow, Teltow, Germany
Andreas Lendlein*
Affiliation:
Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany Helmholtz Virtual Institute - Multifunctional Materials in Medicine, Berlin and Teltow, Teltow, Germany
*
*(Email: [email protected])
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Abstract

The therapeutic effect of mesenchymal stem cells (MSCs) has been investigated in various clinical applications, in which their functional benefits are mainly attributed to the secretion of soluble factors. The enhancement of their therapeutic potential by physical and chemical properties of cell culture substrate is a safe and effective strategy, since they are highly sensitive to their microenvironment such as the elasticity and surface topography. In this study, we demonstrated that the geometry of polymeric substrate regulated the interleukin-6 (IL-6) secretion of human adipose derived MSCs. Polystyrene substrates comprising arrays of square-shaped (S50) or round-shaped (R50) microwells (side length or diameter of 50 μm and depth of 10 μm) were prepared by injection molding. Cellular apoptototic rate of MSCs was not affected by the microwell geometry, while the upregulated secretion of IL-6 and the enhancement of nuclear transcription factor STAT3 were detected in MSCs seeded on S50 substrate. The geometry-dependent modulatory effect was highly associated with ROCK signaling cascade. The inhibition of ROCK abolished the disparity in IL-6 secretion. These findings highlight the possibility to steer the secretion profile of stem cells via microwell geometry in combination with the manipulation of ROCK signaling pathway.

Keywords

microstructurebiomedicalbiological
Type
Articles
Information
MRS Advances , Volume 2 , Issue 47: Soft Materials and Biomaterials , 2017 , pp. 2561 - 2570
Copyright
Copyright © Materials Research Society 2017 

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