title: Differential regulation of stiffness, topography, and dimension of substrates in rat mesenchymal stem cells.
abstract: The physiological microenvironment of the stem cell niche, including the three factors of stiffness, topography, and dimension, is crucial to stem cell proliferation and differentiation. Although a growing body of evidence is present to elucidate the importance of these factors individually, the interaction of the biophysical parameters of the factors remains insufficiently characterized, particularly for stem cells. To address this issue fully, we applied a micro-fabricated polyacrylamide hydrogel substrate with two elasticities, two topographies, and three dimensions to systematically test proliferation, morphology and spreading, differentiation, and cytoskeletal re-organization of rat bone marrow mesenchymal stem cells (rBMSCs) on twelve cases. An isolated but not combinatory impact of the factors was found regarding the specific functions. Substrate stiffness or dimension is predominant in regulating cell proliferation by fostering cell growth on stiff, unevenly dimensioned substrate. Topography is a key factor for manipulating cell morphology and spreading via the formation of a large spherical shape in a pillar substrate but not in a grooved substrate. Although stiffness leads to osteogenic or neuronal differentiation of rBMSCs on a stiff or soft substrate, respectively, topography or dimension also plays a lesser role in directing cell differentiation. Neither an isolated effect nor a combinatory effect was found for actin or tubulin expression, whereas a seemingly combinatory effect of topography and dimension was found in manipulating vimentin expression. These results further the understandings of stem cell proliferation, morphology, and differentiation in a physiologically mimicking microenvironment.
authors.affiliation: Center of Biomechanics and Bioengineering and Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Li
authors.forename: Yuanwei
authors.initials: Y
authors.lastname: Gong
authors.forename: Shujin
authors.initials: S
authors.lastname: Sun
authors.forename: Yu
authors.initials: Y
authors.lastname: Du
authors.forename: Dongyuan
authors.initials: D
authors.lastname: Lü
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Liu
authors.forename: Mian
authors.initials: M
authors.lastname: Long
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D005434:Flow Cytometry; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051381:Rats; D013234:Stem Cells / Q000166:cytology*
keywords: Differentiation; Dimension; Proliferation; Stem cell; Stiffness; Topography