title: Controlling major cellular processes of human mesenchymal stem cells using microwell structures.
abstract: Directing stem cells towards a desired location and function by utilizing the structural cues of biomaterials is a promising approach for inducing effective tissue regeneration. Here, the cellular response of human adipose-derived mesenchymal stem cells (hADSCs) to structural signals from microstructured substrates comprising arrays of square-shaped or round-shaped microwells is explored as a transitional model between 2D and 3D systems. Microwells with a side length/diameter of 50 μm show advantages over 10 μm and 25 μm microwells for accommodating hADSCs within single microwells rather than in the inter-microwell area. The cell morphologies are three-dimensionally modulated by the microwell structure due to differences in focal adhesion and consequent alterations of the cytoskeleton. In contrast to the substrate with 50 μm round-shaped microwells, the substrate with 50 μm square-shaped microwells promotes the proliferation and osteogenic differentiation potential of hADSCs but reduces the cell migration velocity and distance. Such microwell shape-dependent modulatory effects are highly associated with Rho/ROCK signaling. Following ROCK inhibition, the differences in migration, proliferation, and osteogenesis between cells on different substrates are diminished. These results highlight the possibility to control stem cell functions through the use of structured microwells combined with the manipulation of Rho/ROCK signaling.
authors.affiliation: Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Kantstraße 55, 14513, Teltow, Germany; Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustraße 3, 14195, Berlin, Germany.
authors.forename: Xun
authors.initials: X
authors.lastname: Xu
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wang
authors.forename: Karl
authors.initials: K
authors.lastname: Kratz
authors.forename: Liang
authors.initials: L
authors.lastname: Fang
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Li
authors.forename: Andreas
authors.initials: A
authors.lastname: Kurtz
authors.forename: Nan
authors.initials: N
authors.lastname: Ma
authors.forename: Andreas
authors.initials: A
authors.lastname: Lendlein
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D001672:Biocompatible Materials / Q000494:pharmacology; D018929:Cell Culture Techniques / Q000379:methods*; D002468:Cell Physiological Phenomena / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D019096:Vitronectin / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D019096:Vitronectin; D054460:rho-Associated Kinases
keywords: differentiation; mesenchymal stem cells; microwells; migration