hASCs外泌体治疗SD大鼠骨质疏松效果评估OA
Evaluation of hASCs exosome therapy for osteoporosis in SD rats
目的:探讨人脂肪间充质干细胞(human adipose-derived mesenchymal stem cells,hASCs)来源外泌体在SD大鼠骨质疏松模型(ovariectomized,OVX)治疗效果评估,简述hASCs来源外泌体在绝经后SD大鼠骨质疏松作用.方法:采用组织块研磨消化法提取hASCs,超速梯度离心法提取脂肪间充质干细胞来源外泌体,透射电镜TEM和纳米粒度分析追踪仪对外泌体进行表征.通过双侧卵巢摘除手术构建雌激素缺乏骨质疏松SD大鼠模型,术后4周,将大鼠随机分组,隔天行股骨颈近端髋关节注射1次,共注射4周后,收集大鼠股骨,拍摄显微CT,分析骨参数.收集大鼠肝脏、肾脏、骨髓、肌肉的病理切片进行H&E染色,评估外泌体注射的可行性,ELISA分析E2和TNF-α与血清骨钙素水平.结果:成功提取hASCs外泌体,并符合外泌体的形态表征,注射hASCs外泌体的OVX大鼠较注射PBS的OVX大鼠股骨骨小梁更为稳定,骨密度上升,并与假手术Sham+PBS组相比并未出现明显的骨密度降低.注射4周后OVX大鼠肝脏、肾脏、骨髓、肌肉的病理切片与sham组相比未发生病理改变,血清骨钙素和TNF-α结果具有一定差异.结论:hASCs外泌体能减轻OVX大鼠骨质疏松的发生进展,可能通过抑制TNF-α介导的炎症反应,同时上调骨钙素水平从而改善骨代谢失衡,这些发现为 hASCs外泌体作为一种新的治疗手段在骨质疏松症的进程中提供新的见解.
Objective:To investigate the therapeutic potential of exosomes derived from human adipose-derived mesenchymal stem cells(hASCs)in treating osteoporosis in Sprague-Dawley(SD)rats(ovariectomized,OVX),and provides a concise over-view of their effects on postmenopausal osteoporosis in SD rats.Methods:hASCs were isolated using tissue block grinding diges-tion,while exosomes were extracted via ultracentrifugation.The characteristics of the exosomes were confirmed using transmis-sion electron microscopy(TEM)and nanoparticle size analysis.The osteoporosis model of SD rats was constructed by bilateral ovariectomy.Four weeks post-surgery,the rats were randomly allocated into groups and received injections into the proximal hip joint of the femoral neck every other day over a 4-week period.Following this,the femurs were harvested and analyzed using micro-computed tomography(micro-CT)to evaluate bone parameters.Hematoxylin and eosin(H&E)staining was performed on liver,kidney,bone marrow,and muscle tissues to assess the safety of exosome injection.Enzyme-linked immunosorbent assay(ELISA)was employed to measure estradiol(E2),TNF-α,and serum osteocalcin levels.Results:hASC-derived exosomes were successfully isolated and exhibited typical exosome morphology.OVX rats treated with hASC exosomes demonstrated more stable femoral trabeculae compared to those receiving PBS,along with increased bone mineral density.Additionally,no significant reduction in bone mineral density was observed in the sham+PBS group compared to the OVX group.Pathological evaluations of liver,kidney,bone marrow,and muscle tissues four weeks after injection revealed no abnormalities when compared to the sham group.Differences were noted in serum osteocalcin and TNF-α levels.Conclusion:Exosomes isolated from human adipose stem cells(hASCs)have the ability to mitigate the development and progression of osteoporosis in OVX rats.This effect might be at-tributed to the suppression of TNF-α-driven inflammation and the enhancement of osteocalcin expression,which stimulates bone formation and helps restore balance to bone metabolism.These results offer valuable perspectives on the therapeutic potential of hASCs-derived exosomes for managing osteoporosis.
曹坤;郭鑫;华鹏冰;李通;刘新宇;高竟彪;陈文健;崔红旺
海南医科大学第一附属医院急诊和创伤外科,海南 海口 570102||海南医科大学第一附属医院急救与创伤研究教育部重点实验室,海南 海口 570100海南医科大学第一附属医院急诊和创伤外科,海南 海口 570102海南医科大学第一附属医院急诊和创伤外科,海南 海口 570102||海南医科大学第一附属医院急救与创伤研究教育部重点实验室,海南 海口 570100海南医科大学第一附属医院急诊和创伤外科,海南 海口 570102海南医科大学第一附属医院急诊和创伤外科,海南 海口 570102海南医科大学第一附属医院急诊和创伤外科,海南 海口 570102海南医科大学第一附属医院急诊和创伤外科,海南 海口 570102海南医科大学第一附属医院急诊和创伤外科,海南 海口 570102||海南医科大学第一附属医院急救与创伤研究教育部重点实验室,海南 海口 570100
医药卫生
脂肪间充质干细胞外泌体骨质疏松治疗
Adipose-derived mesenchymal stem cellsExosomesOsteoporosisTreatment
《海南医科大学学报》 2026 (9)
641-648,8
This study was supported by the Key Research and Development Project of Hainan Province(ZDYF2024 SHFZ137)Hainan Provincial Natural Science Foundation High level Talent Project(822RC827)2024 Hainan Province Graduate Innovation Research Project(Qhys2024-436) 海南省重点研发项目(ZDYF2024SHFZ137)海南省自然科学基金高层次人才项目(822RC827)2024年海南省研究生创新科研课题(Qhys2024-436)
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