2. Academic Validation
  3. Sea buckthorn-derived extracellular vesicles foster bone regeneration through aau-miR168-mediated pathways

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

  • Stem Cell Res Ther. 2025 Jun 3;16(1):281. doi: 10.1186/s13287-025-04373-8.
Mai Zhao # 1 2,  Xiaolin Chen # 2,  Wenyan Wang 2,  Mengying Li 2,  Hui Zhang 2,  Xiuqun Zou 2,  Jiamin Wang 2,  Qian Cong 3,  Xingyuan Ma 4,  Zhaoyuan Hou 5 6,  Haodong Lin 7,  Hao Jia 8 9
Affiliations

Affiliations

  • 1 Trauma Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, New Songjiang Road 650, Shanghai, 201620, China.
  • 2 Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.
  • 3 Department of Biomedical Sciences, College of Dentistry, Texas A&M University, 3302 Gaston Avenue, Room 455, Dallas, TX, 75246, USA.
  • 4 State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.
  • 5 Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China. houzy@sjtu.edu.cn.
  • 6 Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cellular Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. houzy@sjtu.edu.cn.
  • 7 Trauma Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, New Songjiang Road 650, Shanghai, 201620, China. haodonglin@hotmail.com.
  • 8 Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China. fonney@sjtu.edu.cn.
  • 9 Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cellular Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. fonney@sjtu.edu.cn.
  • # Contributed equally.
PMID: 40462231 DOI: 10.1186/s13287-025-04373-8
Abstract

Background: Plant-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.

Methods: SAEVs 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.

Results: SAEVs 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.

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

Keywords

Bone marrow mesenchymal stromal cell; Extracellular vesicle; Osteocalcin; Osteogenesis; Runx2; Sea buckthorn.

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