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 α2 and β1 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 β-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.
