Journal of nanobiotechnologyFeb 21, 2026

Small vesicles from healthy bone stem cells help bone healing by carrying the anti-aging factor JMJD6

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Updated Feb 23, 2026

Abstract

Extracellular vesicles (EVs) from bone marrow mesenchymal stem cells (BMSCs) can be optimized for osteogenic efficacy by delaying cellular senescence through a niche-mimicking culture system.

Cellular senescence in BMSCs significantly alters their secretome and affects the osteogenic potential of both the cells and their derived EVs.
A niche-mimicking culture system was developed to maintain cellular homeostasis and delay senescence in BMSCs.
Single cell transcriptome analysis showed that this culture system enhanced the expression of homeostasis-related genes.
Small extracellular vesicles (sEVs) from homeostatic BMSCs demonstrated greater osteogenic stimulation and improved bone defect repair compared to those from conventional monolayer cultures.
Key homeostasis-related genes, including JMJD6, LIF, CYP19A1, and LAMA1, were identified as functioning throughout the process and contributing to the 'homeostatic phenotype' of BMSCs.
JMJD6 was highlighted as a crucial gene that has anti-senescence properties and promotes osteogenesis via the Wnt pathway in BMSCs.

Simplified

The therapeutic efficacy of extracellular vesicles (EVs) depends on the status of their donor cells. Cellular senescence of bone marrow mesenchymal stem cells (BMSCs), which induces significant changes to cellular secretome, greatly affects the osteogenesis of the donor BMSCs along with BMSC-derived EVs. Stem cells prefer a homeostatic self-renewing state to alleviate the senescence and loss of stemness caused by external disturbance, but which inevitable in EV produce. In this study, to avoid the senescence of BMSCs caused by in vitro culture and boost the osteogenesis efficacy of BMSC-derived small extracellular vesicles (sEVs), we established a niche-mimicking (NM) culturing system to maintain the cellular homeostasis that significantly delayed stem cell senescence in vitro. As a result, single cell transcriptome revealed that NM-culturing significantly enhanced the expression level of the homeostasis-related genes. Then we found that sEVs produced by homeostatic BMSCs exhibited superior osteogenic stimulation efficacy and bone defect repair compared to those from conventional monolayer-cultured BMSCs. Mechanically, by analyzing the "shuttling effect" of sEVs via multi-omic analysis, we found that the key homeostasis-related genes (including JMJD6, LIF, CYP19A1, and LAMA1) functioned throughout the entire process, by thus we defined the "homeostatic phenotype" of BMSC. Among the identified homeostasis-related genes in sEVs, JMJD6 emerges as a key gene, exhibiting anti-senescence characteristics and stimulating osteogenesis via Wnt pathway in BMSCs. This study optimizes the production part of stem cell-based EV therapy by maintaining the cellular homeostasis of donor cells, which delays cell senescence and boosts the osteogenesis stimulation of EVs, and JMJD6 is a key homeostasis-related gene that regulated cell senescence and osteogenesis of BMSC.

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Competing interests

Declarations. Ethics approval and consent to participate: Obtaining samples of hBMSCs was reviewed and approved by Ethics Committee of the First Hospital of Jilin University (No. 22K095-002). The animal experiment was reviewed and approved by the Animal Protection and Utilization Committee of Changchun Weishi Testing Technology Service (No. 20230109-01). Consent for publication: All authors agree to be published. Competing interests: The authors declare no competing interests.

PubMed

Small vesicles from healthy bone stem cells help bone healing by carrying the anti-aging factor JMJD6

Abstract

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