The effect of matrix stiffness on the differentiation of mesenchymal stem cells in response to TGF-β

Jennifer S. Park, Julia S. Chu, Anchi D. Tsou, Rokhaya Diop, Zhenyu Tang, Aijun Wang, Song Li

Research output: Contribution to journalArticle

398 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3921-3930
Number of pages10
JournalBiomaterials
Volume32
Issue number16
DOIs
StatePublished - Jun 2011

Fingerprint

Transforming Growth Factors
Stiffness matrix
Stem cells
Mesenchymal Stromal Cells
Substrates
Cell Adhesion
Smooth Muscle Myocytes
Stress Fibers
Cell adhesion
Actins
Cell Differentiation
Muscle
rho GTP-Binding Proteins
Regenerative Medicine
Stiffness
Lipoprotein Lipase
Biocompatible Materials
Tissue Engineering
Intercellular Signaling Peptides and Proteins
Regeneration

Keywords

  • Cell adhesion
  • Chondrocyte
  • Extracellular matrix
  • Matrix rigidity
  • Mesenchymal stem cells
  • Smooth muscle cell

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

The effect of matrix stiffness on the differentiation of mesenchymal stem cells in response to TGF-β. / Park, Jennifer S.; Chu, Julia S.; Tsou, Anchi D.; Diop, Rokhaya; Tang, Zhenyu; Wang, Aijun; Li, Song.

In: Biomaterials, Vol. 32, No. 16, 06.2011, p. 3921-3930.

Research output: Contribution to journalArticle

Park, Jennifer S. ; Chu, Julia S. ; Tsou, Anchi D. ; Diop, Rokhaya ; Tang, Zhenyu ; Wang, Aijun ; Li, Song. / The effect of matrix stiffness on the differentiation of mesenchymal stem cells in response to TGF-β. In: Biomaterials. 2011 ; Vol. 32, No. 16. pp. 3921-3930.
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