Evidence map›Paper›PMID 40462231›Full record

ArticleStem cell research & therapy2025

Sea buckthorn-derived extracellular vesicles foster bone regeneration through aau-miR168-mediated pathways.

Mai Zhao, Xiaolin Chen, Wenyan Wang, Mengying Li, Hui Zhang, Xiuqun Zou, Jiamin Wang, Qian Cong, Xingyuan Ma, Zhaoyuan Hou and 2 more

Abstract read
In one paragraph

Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Review
  2. Review
  3. Apple-Derived Vesicles Orchestrate Bone Regeneration:International journal of molecular sciences · 2026
    Article
  4. Review
  5. Review
  6. Review
  7. Review
  8. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Mai Zhao *Trauma Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, New Songjiang Road 650, Shanghai, 201620, China.
Xiaolin Chen *Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.
Wenyan WangFaculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.
Mengying LiFaculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.
Hui ZhangFaculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.
Xiuqun ZouFaculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.
Jiamin WangFaculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.
Qian CongDepartment of Biomedical Sciences, College of Dentistry, Texas A&M University, 3302 Gaston Avenue, Room 455, Dallas, TX, 75246, USA.
Xingyuan MaState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.
Zhaoyuan HouFaculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China. houzy@sjtu.edu.cn.
Haodong LinTrauma Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, New Songjiang Road 650, Shanghai, 201620, China. haodonglin@hotmail.com.
Hao JiaFaculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China. fonney@sjtu.edu.cn.ORCID http://orcid.org/0000-0003-1856-6013

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPlant-derived extracellular vesicles (P-EVs) possess remarkable therapeutic potential, yet the regenerative capabilities of sea buckthorn-derived extracellular vesicles (SAEVs) remain underexplored. This study aims to elucidate the osteogenic and bone-healing properties of SAEVs.

methodsSAEVs were isolated from sea buckthorn juice via differential centrifugation and characterized using electron microscopy and dynamic light scattering. Bone marrow mesenchymal stromal cells (BMSCs) were treated with SAEVs, and cellular uptake was evaluated through fluorescence microscopy and flow cytometry. In vivo, DiD-labeled SAEVs were orally administered to mice to determine biodistribution using IVIS imaging. A murine femoral defect model was employed to assess the bone regenerative efficacy of SAEVs delivered with or without GelMA hydrogels, analyzed by micro-CT and histological staining. Small RNA sequencing identified SAEV-derived miRNAs, and luciferase reporter assays validated the miRNA-mediated regulation of osteogenic genes.

resultsSAEVs efficiently internalized into BMSCs via macropinocytosis, promoting the expression of key osteogenic markers such as Runx2 and osteocalcin. In vivo, SAEV-GelMA hydrogels significantly accelerated bone regeneration in a femoral defect model without inducing adverse hematological effects, affirming the safety of SAEV administration. Mechanistic investigations revealed an enrichment of miRNAs, particularly aau-miR168, which modulates osteogenesis through the aau-miR168/LBH/RUNX2 signaling cascade.

conclusionsThis study highlights SAEVs as a transformative and biocompatible therapeutic strategy for fracture healing and osteoporosis management, offering a novel avenue for regenerative medicine.

Indexed as

Bone RegenerationExtracellular VesiclesHippophaeMicroRNAsAnimalsMaleMesenchymal Stem CellsMiceOsteogenesisMicroRNAsBone marrow mesenchymal stromal cellExtracellular vesicleOsteocalcinOsteogenesisRunx2Sea buckthorn

Identifiers

PMID40462231
PMCPMC12135495

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.