2014
DOI: 10.1371/journal.pone.0102426
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Abstract: Because human mesenchymal stem cells (hMSC) have profound immunomodulatory effects, many attempts have been made to use hMSCs in preclinical and clinical trials. For hMSCs to be used in therapy, a large population of hMSCs must be generated by in vitro expansion. However, the immunomodulatory changes following the in vitro expansion of hMSCs have not been elucidated. In this study, we evaluated the effect of replicative senescence on the immunomodulatory ability of hMSCs in vitro and in vivo. Late-passage hMSC… Show more

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Cited by 60 publications
(71 citation statements)
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“…This result shows that indomethacin interfered with MSCmediated suppression of lymphocytes. The results also indicate that the suppression of MSCs is associated with or mediated by PGE2, which has been previously observed for UCMSCs (Kim et al, 2015;Yu et al, 2014). However, many published publications have also suggested the role of other factors (TGFbeta, HGF, PGE 2 , NO, and IDO) in immune modulation by MSCs (Ma et al, 2014;Soleymaninejadian et al, 2012;Zhao et al, 2016).…”
Section: Discussionsupporting
confidence: 81%
“…This result shows that indomethacin interfered with MSCmediated suppression of lymphocytes. The results also indicate that the suppression of MSCs is associated with or mediated by PGE2, which has been previously observed for UCMSCs (Kim et al, 2015;Yu et al, 2014). However, many published publications have also suggested the role of other factors (TGFbeta, HGF, PGE 2 , NO, and IDO) in immune modulation by MSCs (Ma et al, 2014;Soleymaninejadian et al, 2012;Zhao et al, 2016).…”
Section: Discussionsupporting
confidence: 81%
“…A body of literature shows that MAPK-ERK signaling plays roles in mediating differentiation of MSCs by growth factor-based methods and by mechanical approaches [63,6567]. Other kinases, such as p38 MAPK and Akt, are primarily associated with immunomodulatory function and tissue repair properties of MSCs [68,69]. Indeed, decreased phosphorylation activity of p38 MAPK caused decline in performance of aged MSCs via reduced production of PGE 2 [68].…”
Section: Discussionmentioning
confidence: 99%
“…Other kinases, such as p38 MAPK and Akt, are primarily associated with immunomodulatory function and tissue repair properties of MSCs [68,69]. Indeed, decreased phosphorylation activity of p38 MAPK caused decline in performance of aged MSCs via reduced production of PGE 2 [68]. Interestingly, ectopic expression of any of the MAP kinases (ERK, JNK, or p38) can induce expression of PTGS2 transcript in fibroblasts [70].…”
Section: Discussionmentioning
confidence: 99%
“…Aged MSCs in late passage morphologically changed with flattening and enlargement, increasing the SA--gal activity compared to young MSCs in early passage. Moreover, aged MSCs exhibited a declined immunosuppressive function when CD3/28 and IL-2 were treated to induce the activation and proliferation of T cells [12]. In aged MSCs, proinflammatory stimuli, such as interferon gamma (IFN ) and tumor necrosis factor alpha (TNF ), increased the phosphorylation of the p38 MAPK, and this phosphorylation was associated with the downregulation of cyclooxygenase-2(COX2)/prostaglandin E 2 (PGE 2 ), suggesting the immunomodulatory ability of MSCs gradually declines with consecutive passages via the p38 MAPK alteration of COX2/PGE 2 levels.…”
Section: Ros Oxidative Stress and Cellular Signaling In Mscs Agingmentioning
confidence: 99%