1 research outputs found
Transcriptional profiling of interleukin-2-primed human adipose derived mesenchymal stem cells revealed dramatic changes in stem cells response imposed by replicative senescence
Inflammation is a double-edged sword with both detrimental and
beneficial consequences. Understanding of the mechanisms of crosstalk
between the inflammatory milieu and human adult mesenchymal stem cells
is an important basis for clinical efforts. Here, we investigate changes
in the transcriptional response of human adipose-derived stem cells to
physiologically relevant levels of IL-2 (IL-2 priming) upon replicative
senescence. Our data suggest that replicative senescence might
dramatically impede human mesenchymal stem cell (MSC) function via
global transcriptional deregulation in response to IL-2. We uncovered a
novel senescence-associated transcriptional signature in human
adipose-derived MSCs hADSCs after exposure to pro-inflammatory
environment: significant enhancement of the expression of the genes
encoding potent growth factors and cytokines with anti-inflammatory and
migration-promoting properties, as well as genes encoding angiogenic and
antiapoptotic promoting factors, all of which could participate in the
establishment of a unique microenvironment. We observed transcriptional
up-regulation of critical components of the nitric oxide synthase
pathway (iNOS) in hADSCs upon replicative senescence suggesting, that
senescent stem cells can acquire metastasis-promoting properties via
stem cell-mediated immunosuppression. Our study highlights the
importance of age as a factor when designing cell-based or
pharmacological therapies for older patients and predicts measurable
biomarkers characteristic of an environment that is conducive to cancer
cells invasiveness and metastasis.LM and BGG was supported by grants from the Spanish Ministry of Science
and Innovation (SAF 2010-15239) to BGG and. LMP are supported by FPI
fellowships from the Spanish Ministry, and BGG acknowledges support from
the ``Ramon y Cajal´´ tenure track programme from the Spanish Ministry
of Science and Innovation (RYC2009-04669). AS and AA are fellows of
Bolashak International Scholarship, AA, AN, AS are sponsored by KazNMU
sponsored program.S