Fibroblast-derived extracellular matrix induces chondrogenic differentiation in human adipose-derived mesenchymal stromal/stem cells in vitro

dc.contributor.authorDzobo, Kevin
dc.contributor.authorTurnley, Taegyn
dc.contributor.authorWishart, Andrew
dc.contributor.authorRowe, Arielle
dc.contributor.authorKallmeyer, Karlien
dc.contributor.authorVan Vollenstee, Fiona A.
dc.contributor.authorThomford, Nicholas Ekow
dc.contributor.authorDandara, Collet
dc.contributor.authorChopera, Denis
dc.contributor.authorPepper, Michael Sean
dc.contributor.authorParker, M. Iqbal
dc.contributor.emailmichael.pepper@up.ac.zaen_ZA
dc.date.accessioned2016-08-31T05:36:42Z
dc.date.available2016-08-31T05:36:42Z
dc.date.issued2016-08-03
dc.description.abstractMesenchymal stromal/stem cells (MSCs) represent an area being intensively researched for tissue engineering and regenerative medicine applications. MSCs may provide the opportunity to treat diseases and injuries that currently have limited therapeutic options, as well as enhance present strategies for tissue repair. The cellular environment has a significant role in cellular development and differentiation through cell–matrix interactions. The aim of this study was to investigate the behavior of adipose-derived MSCs (ad-MSCs) in the context of a cell-derived matrix so as to model the in vivo physiological microenvironment. The fibroblast-derived extracellular matrix (fd-ECM) did not affect ad-MSC morphology, but reduced ad-MSC proliferation. Ad-MSCs cultured on fd-ECM displayed decreased expression of integrins 2 and 1 and subsequently lost their multipotency over time, as shown by the decrease in CD44, Octamer-binding transcription factor 4 (OCT4), SOX2, and NANOG gene expression. The fd-ECM induced chondrogenic differentiation in ad-MSCs compared to control ad-MSCs. Loss of function studies, through the use of siRNA and a mutant Notch1 construct, revealed that ECM-mediated ad-MSCs chondrogenesis requires Notch1 and -catenin signaling. The fd-ECM also showed anti-senescence effects on ad-MSCs. The fd-ECM is a promising approach for inducing chondrogenesis in ad-MSCs and chondrogenic differentiated ad-MSCs could be used in stem cell therapy procedures.en_ZA
dc.description.departmentImmunologyen_ZA
dc.description.librarianam2016en_ZA
dc.description.sponsorshipThe International Centre for Genetic Engineering and Biotechnology (ICGEB) (Grant Number: 2015/0001), the National Research Foundation (NRF) of South Africa (Grant Number: 91457: RCA13101656402), the Medical Research Council of South Africa in terms of the MRC’s Flagships Awards Project SAMRC-RFA-UFSP-01-2013/STEM CELLS, the SAMRC Extramural Unit for Stem Cell Research and Therapy and the Institute for Cellular and Molecular Medicine, University of Pretoria and the University of Cape Town.en_ZA
dc.description.urihttp://www.mdpi.com/journal/ijmsen_ZA
dc.description.urihttp://www.mdpi.com/1422-0067/17/8/1259/s1en_ZA
dc.identifier.citationDzobo, K, Turnley, T, Wishart, A, Rowe, A, Kallmeyer, K, Van Vollenstee, FA, Thomford, NE, Dandara, C, Chopera, D, Pepper, MS & Parker, MI 2016, 'Fibroblast-derived extracellular matrix induces chondrogenic differentiation in human adipose-derived mesenchymal stromal/stem cells in vitro', International Journal of Molecular Sciences, vol. 17, art. #1259, pp. 1-20.en_ZA
dc.identifier.issn1422-0067
dc.identifier.issn10.3390/ijms17081259
dc.identifier.urihttp://hdl.handle.net/2263/56515
dc.language.isoenen_ZA
dc.publisherMDPI Publishingen_ZA
dc.rights© 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license.en_ZA
dc.subjectRegenerative medicineen_ZA
dc.subjectThree-dimensionalen_ZA
dc.subjectExtracellular matrixen_ZA
dc.subjectDifferentiationen_ZA
dc.subjectChondrogenesisen_ZA
dc.subjectMesenchymal stromal/stem cells (MSCs)en_ZA
dc.subjectFibroblast-derived extracellular matrix (fd-ECM)en_ZA
dc.titleFibroblast-derived extracellular matrix induces chondrogenic differentiation in human adipose-derived mesenchymal stromal/stem cells in vitroen_ZA
dc.typeArticleen_ZA

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