title: Three-dimensional spherical spatial boundary conditions differentially regulate osteogenic differentiation of mesenchymal stromal cells.
abstract: The spatial boundary condition (SBC) arising from the surrounding microenvironment imposes specific geometry and spatial constraints that affect organogenesis and tissue homeostasis. Mesenchymal stromal cells (MSCs) sensitively respond to alterations of mechanical cues generated from the SBC. However, mechanical cues provided by a three-dimensional (3D) environment are deprived in a reductionist 2D culture system. This study investigates how SBC affects osteogenic differentiation of MSCs using 3D scaffolds with monodispersed pores and homogenous spherical geometries. MSCs cultured under SBCs with diameters of 100 and 150 μm possessed the greatest capability of osteogenic differentiation. This phenomenon was strongly correlated with MSC morphology, organization of actin cytoskeleton, and distribution of focal adhesion involving α2 and α5 integrins. Further silencing either α2 or α5 integrin significantly reduced the above mentioned mechanosensitivity, indicating that the α2 and α5 integrins as mechano-sensitive molecules mediate MSCs' ability to provide enhanced osteogenic differentiation in response to different spherical SBCs. Taken together, the findings provide new insights regarding how MSCs respond to mechanical cues from the surrounding microenvironment in a spherical SBC, and such biophysical stimuli should be taken into consideration in tissue engineering and regenerative medicine in conjunction with biochemical cues.
authors.affiliation: Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei 11221, Taiwan.
authors.forename: Yin-Ping
authors.initials: YP
authors.lastname: Lo
authors.affiliation: Stem Cell Research Center, National Yang-Ming University, Taipei 11221, Taiwan.
authors.forename: Yi-Shiuan
authors.initials: YS
authors.lastname: Liu
authors.affiliation: Taiwan International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei 11221, Taiwan.
authors.forename: Marilyn G
authors.initials: MG
authors.lastname: Rimando
authors.affiliation: Center for Stem Cell Research, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan.|Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei 11031, Taiwan.|Department of Ophthalmology, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan.
authors.forename: Jennifer Hui-Chun
authors.initials: JH
authors.lastname: Ho
authors.affiliation: Institute of Physics, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Keng-Hui
authors.initials: KH
authors.lastname: Lin
authors.affiliation: Taipei City Hospital, Taipei 10341, Taiwan.|Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan.|Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
authors.forename: Oscar K
authors.initials: OK
authors.lastname: Lee
mesh_terms: D000199:Actins / Q000378:metabolism; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002470:Cell Survival; D022001:Focal Adhesions; D006801:Humans; D039421:Integrin alpha2 / Q000378:metabolism; D039482:Integrin alpha5 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010012:Osteogenesis; D018874:Spheroids, Cellular; D055153:Stem Cell Niche; D054457:Tissue Scaffolds
chemical_list: D000199:Actins; D039421:Integrin alpha2; D039482:Integrin alpha5