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The effect of matrix stiffness on the differentiation of mesenchymal stem cells in response to TGF-β
Author(s):
Jennifer S. Park
,
Julia S. Chu
,
Anchi D. Tsou
,
Rokhaya Diop
,
Zhenyu Tang
,
Aijun Wang
,
Song Li
Publication date
Created:
June 2011
Publication date
(Print):
June 2011
Journal:
Biomaterials
Publisher:
Elsevier BV
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Abstract
Bone marrow mesenchymal stem cells (MSCs) are a valuable cell source for tissue engineering and regenerative medicine. Transforming growth factor β (TGF-β) can promote MSC differentiation into either smooth muscle cells (SMCs) or chondrogenic cells. Here we showed that the stiffness of cell adhesion substrates modulated these differential effects. MSCs on soft substrates had less spreading, fewer stress fibers and lower proliferation rate than MSCs on stiff substrates. MSCs on stiff substrates had higher expression of SMC markers α-actin and calponin-1; in contrast, MSCs on soft substrates had a higher expression of chondrogenic marker collagen-II and adipogenic marker lipoprotein lipase (LPL). TGF-β increased SMC marker expression on stiff substrates. However, TGF-β increased chondrogenic marker expression and suppressed adipogenic marker expression on soft substrates, while adipogenic medium and soft substrates induced adipogenic differentiation effectively. Rho GTPase was involved in the expression of all aforementioned lineage markers, but did not account for the differential effects of substrate stiffness. In addition, soft substrates did not significantly affect Rho activity, but inhibited Rho-induced stress fiber formation and α-actin assembly. Further analysis showed that MSCs on soft substrates had weaker cell adhesion, and that the suppression of cell adhesion strength mimicked the effects of soft substrates on the lineage marker expression. These results provide insights of how substrate stiffness differentially regulates stem cell differentiation, and have significant implications for the design of biomaterials with appropriate mechanical property for tissue regeneration. Copyright © 2011 Elsevier Ltd. All rights reserved.
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Gamma Delta T cells
Author and article information
Journal
Title:
Biomaterials
Abbreviated Title:
Biomaterials
Publisher:
Elsevier BV
ISSN (Print):
01429612
Publication date Created:
June 2011
Publication date (Print):
June 2011
Volume
: 32
Issue
: 16
Pages
: 3921-3930
Article
DOI:
10.1016/j.biomaterials.2011.02.019
PMC ID:
3073995
PubMed ID:
21397942
SO-VID:
8ea34787-4e4f-4f46-ad4f-9aa59300678b
Copyright ©
© 2011
License:
https://www.elsevier.com/tdm/userlicense/1.0/
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