Nanotopography alters nuclear protein expression, proliferation and differentiation of human mesenchymal stem/stromal cells.

Karina Kulangara,Kam W Leong,Yong Yang,Malathi Chellappan,Jennifer Yang,Stan Gronthos

doi:10.1371/journal.pone.0114698

Karina Kulangara, Kam W Leong + Show 4 more

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https://doi.org/10.1371/journal.pone.0114698

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Journal: PloS one	Publication Date: Dec 18, 2014
Citations: 28	License type: CC BY 4.0

Affiliation: Duke University

Abstract

Mesenchymal stem/stromal cells respond to physical cues present in their microenvironment such as substrate elasticity, geometry, or topography with respect to morphology, proliferation, and differentiation. Although studies have demonstrated the role of focal adhesions in topography-mediated changes of gene expression, information linking substrate topography to the nucleus remains scarce. Here we show by two-dimensional gel electrophoresis and western blotting that A-type lamins and retinoblastoma protein are downregulated in mesenchymal stem/stromal cells cultured on 350 nm gratings compared to planar substrates; these changes lead to a decrease in proliferation and changes in differentiation potential.

Highlights

Mesenchymal stem/stromal cells (MSCs) are an attractive cell source for regenerative medicine applications
Our results are interesting in several aspects: Firstly, we report a decrease in A-type lamin expression in response to substrate nanogratings compared to planar control substrates similar to the scaling of A-type lamins in response to soft substrates recently reported by Swift et al [23]
Our results contrast with the ones described by Swift et al by the fact that they have shown a shift towards adipogenic differentiation, whereas we have shown the opposite trend in response to underlying nanotopography

Summary

Introduction

Mesenchymal stem/stromal cells (MSCs) are an attractive cell source for regenerative medicine applications. MSCs can be readily expanded in vitro and differentiated into the adipogenic, osteogenic, chondrogenic or myogenic lineage [1]–[3]. They can modulate the immune response [4], [5]. MSC therapy often involves the use of a scaffold, either for expansion and differentiation in vitro or direct application in vivo. Scaffold properties such as topography and elasticity can influence the gene expression and differentiation of MSC [6]–[9]. Several recent studies have contributed to our understanding on how MSCs sense

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