Zhao Mai, Chen Xiaolin, Wang Wenyan, Li Mengying, Zhang Hui, Zou Xiuqun, Wang Jiamin, Cong Qian, Ma Xingyuan, Hou Zhaoyuan, Lin Haodong, Jia Hao
Trauma Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, New Songjiang Road 650, Shanghai, 201620, China.
Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.
Stem Cell Res Ther. 2025 Jun 3;16(1):281. doi: 10.1186/s13287-025-04373-8.
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.
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.
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.
This study highlights SAEVs as a transformative and biocompatible therapeutic strategy for fracture healing and osteoporosis management, offering a novel avenue for regenerative medicine.
植物来源的细胞外囊泡（P-EVs）具有显著的治疗潜力，但沙棘来源的细胞外囊泡（SAEVs）的再生能力仍未得到充分探索。本研究旨在阐明SAEVs的成骨和骨愈合特性。
通过差速离心从沙棘汁中分离出SAEVs，并使用电子显微镜和动态光散射进行表征。用SAEVs处理骨髓间充质基质细胞（BMSCs），并通过荧光显微镜和流式细胞术评估细胞摄取情况。在体内，将DiD标记的SAEVs口服给予小鼠，使用IVIS成像确定生物分布。采用小鼠股骨缺损模型评估在有或没有GelMA水凝胶的情况下递送的SAEVs的骨再生效果，通过微型计算机断层扫描（micro-CT）和组织学染色进行分析。小RNA测序鉴定了SAEVs衍生的微小RNA（miRNAs），荧光素酶报告基因测定验证了miRNA介导的对成骨基因的调控。
SAEVs通过巨胞饮作用有效地内化到BMSCs中，促进关键成骨标志物如Runx2和骨钙素的表达。在体内，SAEV-GelMA水凝胶在股骨缺损模型中显著加速了骨再生，且未诱导不良血液学影响，证实了SAEV给药的安全性。机制研究揭示了miRNAs的富集，特别是aau-miR168，其通过aau-miR168/LBH/RUNX2信号级联调节成骨作用。
本研究强调SAEVs是一种用于骨折愈合和骨质疏松症管理的变革性且生物相容性良好治疗策略，为再生医学提供了一条新途径。
