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

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Authors

Dzobo, Kevin
Turnley, Taegyn
Wishart, Andrew
Rowe, Arielle
Kallmeyer, Karlien
Van Vollenstee, Fiona A.
Thomford, Nicholas Ekow
Dandara, Collet
Chopera, Denis
Pepper, Michael Sean

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Publisher

MDPI Publishing

Abstract

Mesenchymal 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.

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Keywords

Regenerative medicine, Three-dimensional, Extracellular matrix, Differentiation, Chondrogenesis, Mesenchymal stromal/stem cells (MSCs), Fibroblast-derived extracellular matrix (fd-ECM)

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Citation

Dzobo, 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.