Mechanism of regulation of stem cell differentiation by matrix stiffness.

Yue Rong,Yulin Li,Lisha Li,Yin Zhang,Hongwei Lv,Meiyu Sun,Li Chen

doi:10.1186/s13287-015-0083-4

Yue Rong, Yulin Li + Show 5 more

Open Access

https://doi.org/10.1186/s13287-015-0083-4

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Journal: Stem cell research & therapy	Publication Date: May 27, 2015
Citations: 365	License type: CC BY 4.0

Affiliation: Jilin University

Abstract

Stem cell behaviors are regulated by multiple microenvironmental cues. As an external signal, mechanical stiffness of the extracellular matrix is capable of governing stem cell fate determination, but how this biophysical cue is translated into intracellular signaling remains elusive. Here, we elucidate mechanisms by which stem cells respond to microenvironmental stiffness through the dynamics of the cytoskeletal network, leading to changes in gene expression via biophysical transduction signaling pathways in two-dimensional culture. Furthermore, a putative rapid shift from original mechanosensing to de novo cell-derived matrix sensing in more physiologically relevant three-dimensional culture is pointed out. A comprehensive understanding of stem cell responses to this stimulus is essential for designing biomaterials that mimic the physiological environment and advancing stem cell-based clinical applications for tissue engineering.

Highlights

Stem cells hold enormous potential for treating a broad spectrum of human diseases due to their multipotency [1,2,3]
We summarize the mechanotransduction steps activated by matrix stiffness in stem cell differentiation (Figure 1)
Mesenchymal stem cell (MSC) cultured on matrices of medium and high stiffness present a large spreading size, well-aligned stress fibers and enhanced focal adhesion assembly, all of which contribute to a high tension state, and promote myogenic and osteogenic differentiation

Summary

Introduction

Stem cells hold enormous potential for treating a broad spectrum of human diseases due to their multipotency [1,2,3]. MSCs cultured on matrices of medium and high stiffness present a large spreading size, well-aligned stress fibers and enhanced focal adhesion assembly, all of which contribute to a high tension state, and promote myogenic and osteogenic differentiation. Lamin-A is likely to bind nuclear actin and influences cell contractility by regulating serum response factor (SRF) pathways, which is known to promote the expression of stress fiber-associated proteins [35,36].

Results

Conclusion