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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
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
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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.

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Articles
Copyright
Copyright © Materials Research Society 2017 

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References

REFERENCES

Galun, E. and Rose-John, S., The regenerative activity of interleukin-6. Methods Mol Biol, 2013. 982: p. 5977.CrossRefGoogle ScholarPubMed
Gu, Y., et al. ., Endogenous IL-6 of mesenchymal stem cell improves behavioral outcome of hypoxic-ischemic brain damage neonatal rats by supressing apoptosis in astrocyte. Sci Rep, 2016. 6: p. 18587.CrossRefGoogle ScholarPubMed
Kyurkchiev, D., et al. ., Secretion of immunoregulatory cytokines by mesenchymal stem cells. World J Stem Cells, 2014. 6(5): p. 552–70.CrossRefGoogle ScholarPubMed
Madrigal, M., Rao, K.S., and Riordan, N.H., A review of therapeutic effects of mesenchymal stem cell secretions and induction of secretory modification by different culture methods. J Transl Med, 2014. 12: p. 260.CrossRefGoogle ScholarPubMed
Engler, A.J., et al. ., Matrix elasticity directs stem cell lineage specification. Cell, 2006. 126(4): p. 677–89.CrossRefGoogle ScholarPubMed
Kilian, K.A., et al. ., Geometric cues for directing the differentiation of mesenchymal stem cells. Proc Natl Acad Sci U S A, 2010. 107(11): p. 4872–7.CrossRefGoogle ScholarPubMed
Xu, X., et al. ., Controlling major cellular processes of human mesenchymal stem cells using microwell structures. Adv Healthc Mater, 2014. 3(12): p. 19912003.CrossRefGoogle ScholarPubMed
Abagnale, G., et al. ., Surface topography enhances differentiation of mesenchymal stem cells towards osteogenic and adipogenic lineages. Biomaterials, 2015. 61: p. 316–26.CrossRefGoogle ScholarPubMed
Pricola, K.L., et al. ., Interleukin-6 maintains bone marrow-derived mesenchymal stem cell stemness by an ERK1/2-dependent mechanism. J Cell Biochem, 2009. 108(3): p. 577–88.CrossRefGoogle Scholar
Cressman, D.E., et al. ., Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice. Science, 1996. 274(5291): p. 1379–83.CrossRefGoogle ScholarPubMed
Crisostomo, P.R., et al. ., Gender differences in injury induced mesenchymal stem cell apoptosis and VEGF, TNF, IL-6 expression: role of the 55 kDa TNF receptor (TNFR1). J Mol Cell Cardiol, 2007. 42(1): p. 142–9.CrossRefGoogle ScholarPubMed
Chen, C.S., et al. ., Geometric control of cell life and death. Science, 1997. 276(5317): p. 1425–8.CrossRefGoogle ScholarPubMed
Yang, J., et al. ., Unphosphorylated STAT3 accumulates in response to IL-6 and activates transcription by binding to NFkappaB. Genes Dev, 2007. 21(11): p. 1396–408.CrossRefGoogle Scholar
Lee, J., et al. ., Interfacial geometry dictates cancer cell tumorigenicity. Nat Mater, 2016. 15(8): p. 856–62.CrossRefGoogle ScholarPubMed
Song, W., et al. ., Adipogenic differentiation of individual mesenchymal stem cell on different geometric micropatterns. Langmuir, 2011. 27(10): p. 6155–62.CrossRefGoogle ScholarPubMed
Pellegrin, S. and Mellor, H., Actin stress fibres. J Cell Sci, 2007. 120(Pt 20): p. 3491–9.CrossRefGoogle ScholarPubMed
Tojkander, S., Gateva, G., and Lappalainen, P., Actin stress fibers–assembly, dynamics and biological roles. J Cell Sci, 2012. 125(Pt 8): p. 1855–64.Google ScholarPubMed
Raptis, L., et al. ., The R(h)oads to Stat3: Stat3 activation by the Rho GTPases. Exp Cell Res, 2011. 317(13): p. 1787–95.CrossRefGoogle Scholar
Ma, W., et al. ., RhoE/ROCK2 regulates chemoresistance through NF-kappaB/IL-6/ STAT3 signaling in hepatocellular carcinoma. Oncotarget, 2016. 7(27): p. 4144541459.CrossRefGoogle ScholarPubMed