ArticleCell communication and signaling : CCS2025
Mesenchymal stem cell derived extracellular vesicles reverses neural aging via OSKM modulation.
Article in Cell communication and signaling : CCS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Brain organoids as models of extracellular vesicle-mediated human neural communication.Neural regeneration research · 2026Article
- Beyond wound closure: translational opportunities and barriers of mesenchymal stem cells and their extracellular vesicles in burn management.Frontiers in cell and developmental biology · 2026Review
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11 authors.
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Abstract
backgroundIntravenously infused human placenta-derived mesenchymal stem cells enhance overall function and exhibit therapeutic potential even with minimal engraftment or tissue replacement, with substances released from human placenta-derived mesenchymal stem cells playing a significant role in these positive outcomes. Stem cell-derived extracellular vesicles transfer beneficial factors that aid recovery in various tissues through genetic regulation. However, the effects of systemically injected mesenchymal stem cells and their released derivatives on normal aging have not been reported.
methodsAged female mice received intravenous infusions of human placenta-derived mesenchymal stem cells. Starting at 18-19 months of age, mice were given injections of either human placenta-derived mesenchymal stem cells or PBS, followed by two more injections at six-week intervals. For the in vitro study, human fetal neural progenitor cells were sourced from spontaneously aborted fetal brain tissue. Extracellular vesicles were isolated from the human placenta-derived mesenchymal stem cell culture media using the qEV original size exclusion column.
resultsRNA sequencing showed human placenta-derived mesenchymal stem cells' effectiveness in modulating aging-related neural pathways, particularly by downregulating age-specific genes in the hippocampus, indicative of neural reactivation. A pivotal aspect of our study was the discovery of micro RNAs in human placenta-derived extracellular vesicles reactivating senescent cells, likely through inhibition of Toll-like receptor 4 signaling and a concomitant increase in OSKM (OCT4, SOX2, KLF4, C-MYC) transcription factors, notably SOX2. The regeneration process involves targeted miRNAs modulating Toll-like receptor 4 and messenger RNAs boosting OSKM levels.
conclusionsOur study represents a pioneering achievement in regenerative medicine, demonstrating the potential of micro RNAs in EVs to stimulate OSKM, a significant stride forward in addressing neural aging.
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