biostudies-literatureUnknown53Ma SNational Natural Science Foundation of ChinaHuman umbilical cord-derived mesenchymal stem cells (hUC-MSCs) transplantation is a promising therapy for Alzheimer's disease (AD). However, hUC-MSCs cultured in vitro easily exhibit replicative senescence, which restricts their application. Although MG53 protein demonstrates multiple roles for a variety of cells and tissues repair, it remains unknown whether MG53 could rejuvenate senescent hUC-MSCs and enhance their efficacy in AD model. Here, we firstly presented that MG53 reinstated senescent hUC-MSCs via the activation of the Nrf2 signaling pathway by increasing cell proliferation and migration, ameliorating senescence and oxidative stress, and decreasing the release of senescence-associated secretory phenotype. In vivo studies showed that MG53 treatment improved the therapeutic effectRedox biology102325https://www.ebi.ac.uk/biostudies/studies/S-EPMC9079718biostudies-literatureMG53 protein rejuvenates hUC-MSCs and facilitates their therapeutic effects in AD mice by activating Nrf2 signaling pathway.PMC9079718Ma SLi ZGuan FWang YShi JZhou XfalseMG53 protein rejuvenates hUC-MSCs and facilitates their therapeutic effects in AD mice by activating Nrf2 signaling pathway.Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) transplantation is a promising therapy for Alzheimer's disease (AD). However, hUC-MSCs cultured in vitro easily exhibit replicative senescence, which restricts their application. Although MG53 protein demonstrates multiple roles for a variety of cells and tissues repair, it remains unknown whether MG53 could rejuvenate senescent hUC-MSCs and enhance their efficacy in AD model. Here, we firstly presented that MG53 reinstated senescent hUC-MSCs via the activation of the Nrf2 signaling pathway by increasing cell proliferation and migration, ameliorating senescence and oxidative stress, and decreasing the release of senescence-associated secretory phenotype. In vivo studies showed that MG53 treatment improved the therapeutic effect2022-01-01T00:00:00Z2022 Jul2025-06-01T02:21:33.841Z2024-11-14T19:57:42.623ZS-EPMC90797183552502610.1016/j.redox.2022.102325