Nrf2 modulates immunosuppressive ability and cellular senescence of human umbilical cord mesenchymal stem cells.
Biochem Biophys Res Commun
; 526(4): 1021-1027, 2020 06 11.
Article
em En
| MEDLINE
| ID: mdl-32317184
ABSTRACT
In the application of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) as clinical therapeutics, long term cells ex vivo expansion results in decline in their function. It has been widely concerned that cellular senescence is associated with UC-MSCs immunomodulatory ability. In this study, we evaluated the effects of consecutive passages on cellular senescence and the immunomodulatory abilities of UC-MSCs. Long term-cultured UC-MSCs showed decreased proliferation, senescence phenotypes and impaired immunosuppressive effects on PHA induced peripheral blood mononuclear cell (PBMC) proliferation. We found that Nrf2, a transcription factor that responds to oxidative stress, that showed decreased expression in long term-cultured UC-MSCs, and the further knock-down of Nrf2 in UC-MSCs induced premature senescence, decreased proliferation ability and immunosuppressive abilities. Furthermore, the protein expression of IDO-1 were decreased in response to the downregulation of Nrf2 in UC-MSCs, suggesting that Nrf2 regulates the immunosuppressive properties of UC-MSCs via Nrf2-mediated IDO-1 expression. In conclusion, our results demonstrate that Nrf2 plays a key role in the regulation of the immunosuppressive properties of UC-MSCs, and we suggest that these findings might provide a strategy to enhance the functionality of UC-MSCs for use in therapeutic applications.
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Base de dados:
MEDLINE
Assunto principal:
Cordão Umbilical
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Terapia de Imunossupressão
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Senescência Celular
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Fator 2 Relacionado a NF-E2
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Células-Tronco Mesenquimais
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article