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

  • Xun Xu (a1) (a2), Weiwei Wang (a1), Zhengdong Li (a1) (a2), Karl Kratz (a1) (a3), Nan Ma (a1) (a2) (a3) and Andreas Lendlein (a1) (a2) (a3)...

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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1. Galun, E. and Rose-John, S., The regenerative activity of interleukin-6. Methods Mol Biol, 2013. 982: p. 5977.
2. 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.
3. Kyurkchiev, D., et al. ., Secretion of immunoregulatory cytokines by mesenchymal stem cells. World J Stem Cells, 2014. 6(5): p. 552–70.
4. 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.
5. Engler, A.J., et al. ., Matrix elasticity directs stem cell lineage specification. Cell, 2006. 126(4): p. 677–89.
6. 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.
7. Xu, X., et al. ., Controlling major cellular processes of human mesenchymal stem cells using microwell structures. Adv Healthc Mater, 2014. 3(12): p. 19912003.
8. Abagnale, G., et al. ., Surface topography enhances differentiation of mesenchymal stem cells towards osteogenic and adipogenic lineages. Biomaterials, 2015. 61: p. 316–26.
9. 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.
10. Cressman, D.E., et al. ., Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice. Science, 1996. 274(5291): p. 1379–83.
11. 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.
12. Chen, C.S., et al. ., Geometric control of cell life and death. Science, 1997. 276(5317): p. 1425–8.
13. 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.
14. Lee, J., et al. ., Interfacial geometry dictates cancer cell tumorigenicity. Nat Mater, 2016. 15(8): p. 856–62.
15. Song, W., et al. ., Adipogenic differentiation of individual mesenchymal stem cell on different geometric micropatterns. Langmuir, 2011. 27(10): p. 6155–62.
16. Pellegrin, S. and Mellor, H., Actin stress fibres. J Cell Sci, 2007. 120(Pt 20): p. 3491–9.
17. 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.
18. 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.
19. Ma, W., et al. ., RhoE/ROCK2 regulates chemoresistance through NF-kappaB/IL-6/ STAT3 signaling in hepatocellular carcinoma. Oncotarget, 2016. 7(27): p. 4144541459.

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