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Extracellular matrix (ECM) plays a very important role in regulating cell function and fate. It is highly desirable to fabricate biomimetic models to investigate the role of ECM in stem cell differentiation. In this study, arginine–glycine–aspartate (RGD)-modified gold nanoparticles (Au NPs) with tunable surface ligand density were prepared to mimic the ECM microenvironment. Their effect on osteogenic and adipogenic differentiation of human mesenchymal stem cells (MSCs) was investigated. The biomimetic Au NPs were taken up by MSCs in a ligand density-dependent manner. The biomimetic NPs with a high RGD density had an inhibitive effect on the alkaline phosphatase (ALP) activity, calcium deposition, and osteogenic marker gene expression of MSCs. Their effect on oil droplet formation and adipogenic marker gene expression was negative when RGD density was low, while their effect was promotive when RGD density was high. The biomimetic Au NPs regulated the osteogenic and adipogenic differentiation of MSCs mainly through affecting the focal adhesion and cytoskeleton. This study highlights the roles of biomimetic NPs on stem cell differentiation that could provide a meaningful strategy in fabricating functional biomaterials for tissue engineering and biomedical applications.


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Ligand density-dependent influence of arginine–glycine–aspartate functionalized gold nanoparticles on osteogenic and adipogenic differentiation of mesenchymal stem cells

Show Author's information Jingchao Li1,2Ying Chen1,2Naoki Kawazoe1,3Guoping Chen1,2,3( )
International Center for Materials NanoarchitectonicsNational Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki, 305-0044Japan
Department of Materials Science and EngineeringGraduate School of Pure and Applied SciencesUniversity of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577Japan
Research Center for Functional MaterialsNational Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki, 305-0044Japan

Abstract

Extracellular matrix (ECM) plays a very important role in regulating cell function and fate. It is highly desirable to fabricate biomimetic models to investigate the role of ECM in stem cell differentiation. In this study, arginine–glycine–aspartate (RGD)-modified gold nanoparticles (Au NPs) with tunable surface ligand density were prepared to mimic the ECM microenvironment. Their effect on osteogenic and adipogenic differentiation of human mesenchymal stem cells (MSCs) was investigated. The biomimetic Au NPs were taken up by MSCs in a ligand density-dependent manner. The biomimetic NPs with a high RGD density had an inhibitive effect on the alkaline phosphatase (ALP) activity, calcium deposition, and osteogenic marker gene expression of MSCs. Their effect on oil droplet formation and adipogenic marker gene expression was negative when RGD density was low, while their effect was promotive when RGD density was high. The biomimetic Au NPs regulated the osteogenic and adipogenic differentiation of MSCs mainly through affecting the focal adhesion and cytoskeleton. This study highlights the roles of biomimetic NPs on stem cell differentiation that could provide a meaningful strategy in fabricating functional biomaterials for tissue engineering and biomedical applications.

Keywords: arginine–glycine–aspartate (RGD) density, biomimetic gold nanoparticles (Au NPs), osteogenic differentiation, adipogenic differentiation, mesenchymal stem cells

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Publication history
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Acknowledgements

Publication history

Received: 24 April 2017
Revised: 18 June 2017
Accepted: 22 June 2017
Published: 02 February 2018
Issue date: March 2018

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany 2017

Acknowledgements

Acknowledgements

This work was supported by the World Premier International Research Center Initiative (WPI) on Materials Nanoarchitectonics from the Ministry of Education, Culture, Sports, Science and Technology, Japan and JSPS KAKENHI Grant Number 15H03027.

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