title: Osteogenic Lineage Commitment of Adipose-Derived Stem Cells Is Predetermined by Three-Dimensional Cell Accumulation on Micropatterned Surface.
abstract: Lineage commitment of stem cells is mainly regulated by their microenvironments, which comprise soluble growth factors, extracellular matrix, mechanical forces, and cell density. Although numerous studies have investigated stem cell response to these factors in two-dimensional (2D) culture, little is known about that in 3D culture. Here, we studied effects of 3D cell accumulation levels on the differentiation behavior of mesenchymal stem cells (MSCs) by using a micropatterned surface. After induction of 3D-cultured MSCs on the surface, their osteogenic differentiation was significantly promoted, while adipogenic differentiation was not. This differentiation behavior of densely packed MSCs in 3D culture is unlike that in 2D culture. Moreover, to determine the contributing factor of this commitment, the relationship between 3D cell accumulation levels and their differentiation potential was studied before differentiation induction. A series of MSCs with varied 3D accumulation levels were constructed on the micropatterned surface, where the accumulated MSCs were not in hypoxic environment. Interestingly, with increasing 3D accumulation levels, MSCs enhanced their osteogenic potential but repressed adipogenic potential in the gene expression level. These results suggest that preconditioned 3D microenvironments with high cell accumulation levels promote osteogenic differentiation of MSCs and their accumulation levels help in regulating MSC differentiation.
authors.affiliation: Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo , Shirokanedai 4-6-1, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Furuhata
authors.forename: Toru
authors.initials: T
authors.lastname: Yoshitomi
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kikuchi
authors.forename: Miho
authors.initials: M
authors.lastname: Sakao
authors.forename: Keitaro
authors.identifier: http://orcid.org/0000-0002-6052-1399
authors.initials: K
authors.lastname: Yoshimoto
mesh_terms: D050156:Adipogenesis; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D059630:Mesenchymal Stem Cells; D010012:Osteogenesis; D013234:Stem Cells
keywords: adipose-derived stem cells; cell accumulation; cell differentiation; mesenchymal stem cells; micropatterned surface; osteogenic potential; poly(ethylene glycol)