@article{discovery10064406,
            year = {2016},
          volume = {31},
           month = {April},
         journal = {European Cells and Materials},
           pages = {221--235},
           title = {Differences in human mesenchymal stem cell secretomes during chondrogenic induction},
            note = {This is the published version of record. For information on re-use, please refer to the publisher's terms and conditions.},
          author = {Gardner, OFW and Fahy, N and Alini, M and Stoddart, MJ},
             url = {https://doi.org/10.22203/eCM.v031a15},
        abstract = {Mesenchymal stem cells (MSCs) can be induced towards
chondrogenesis through the application of chondrogenic
stimuli such as transforming growth factor-{\ensuremath{\beta}} (TGF-{\ensuremath{\beta}}) or
by multiaxial mechanical load. Previous work has showed
that the chondrogenic effect of multiaxial load on MSCs
is mediated by the endogenous production of TGF-{\ensuremath{\beta}}1
by stimulated cells. This work compared the effects of
TGF-{\ensuremath{\beta}}1 stimulation and multiaxial mechanical load on
the secretomes of stimulated cells. MSCs were seeded into
fibrin-poly(ester-urethane) scaffolds and chondrogenically
stimulated with either TGF-{\ensuremath{\beta}}1 or mechanical load.
The culture media was collected and analysed for 174
proteins using a cytokine antibody array. The results of
the secretome analysis were then confirmed at a gene
expression level by real-time PCR. As results implicated
nitric oxide (NO), the media nitrite content was also
determined as an indirect measurement of media NO levels.
Results showed that TGF-{\ensuremath{\beta}}1 stimulation and mechanical
load lead to similar changes in factors such as BLC, VEGF
and MMP13, whilst differences in detected levels were
seen for factors including leptin, MDC, MIP3{\ensuremath{\alpha}} and LAP.
Gene expression analysis confirmed significant changes
in four factors: angiopoietin 2, GRO{\ensuremath{\alpha}}, MMP13 and
osteoprotegerin. After one week in culture the media nitrite
content was significantly higher in loaded groups than
both control and TGF-{\ensuremath{\beta}}1 stimulated groups, suggesting
this may be a major therapeutic target. These data show
that despite clear similarities, TGF-{\ensuremath{\beta}}1 stimulation and load
have distinct effects on MSCs and are not analogous. This
study has identified a number of potentially novel targets
for tissue engineering, these data may also be useful for
improving rehabilitation protocols e.g. after microfracture.},
            issn = {1473-2262},
        keywords = {Secretome, paracrine signalling, regenerative
medicine, cartilage repair, cytokines.}
}