骨髓间充质干细胞来源细胞外囊泡治疗股骨头骨坏死的研究进展

doi:10.3969/j.issn.1006-5725.2025.23.001

Abstract

Abstract:

Osteonecrosis of the femoral head （ONFH） is a disabling orthopedic disease， pathologically characterized by progressive collapse of the femoral head accompanied by destruction of the trabecular and articular cartilage structures， leading to hip joint pain and progressive functional impairment. Bone marrow mesenchymal stem cell-derived extracellular vesicles （BMSC-EVs） show great promise in tissue repair and regeneration， with low immunogenicity and tumorigenicity， and play roles in osteogenesis， angiogenesis， and immunomodulation. This review summarizes the therapeutic effects and underlying mechanisms of BMSC-EVs in ONFH， providing a theoretical basis for its treatment.

Key words: femoral head necrosis, bone marrow mesenchymal stem cells, extracellular vesicles, bone repair

CLC Number:

R274

Aiqiang LI,Ning ZHAO,Xusheng ZHANG,Haiping. LIU. Research progress on the treatment of femoral skull necrosis by extracellular vesicles from bone marrow mesenchymal stem cells[J]. The Journal of Practical Medicine, 2025, 41(23): 3631-3637.

Figures/Tables 1

References 52

[1]	ZAFFAGNINI M， BOFFA A， ANDRIOLO L， et al. Orthobiologic therapies delay the need for hip arthroplasty in patients with avascular necrosis of the femoral head： A systematic review and survival analysis［J］. Knee Surg Sports Traumatol Arthrosc， 2025， 33（3）： 1112-1127. doi:10.1002/ksa.12532 doi: 10.1002/ksa.12532
[2]	ZHANG S， WANG H， MENG Q， et al. Recent advances in osteonecrosis of the femoral head： A focus on mesenchymal stem cells and adipocytes［J］. J Transl Med， 2025， 23（1）： 592. doi:10.1186/s12967-025-06564-6 doi: 10.1186/s12967-025-06564-6
[3]	LEAL A F， PACHAJOA H， TOMATSU S. Mesenchymal Stem Cell-Derived Extracellular Vesicles： Seeking into Cell-Free Therapies for Bone-Affected Lysosomal Storage Disorders［J］. Int J Mol Sci， 2025， 26（13）： 6448. doi:10.3390/ijms26136448 doi: 10.3390/ijms26136448
[4]	ZHENG C， WU Y， XU J， et al. Exosomes from bone marrow mesenchymal stem cells ameliorate glucocorticoid-induced osteonecrosis of femoral head by transferring microRNA-210 into bone microvascular endothelial cells［J］. J Orthop Surg Res， 2023， 18（1）： 939. doi:10.1186/s13018-023-04440-x doi: 10.1186/s13018-023-04440-x
[5]	LI H， LIU H， ZHOU Y， et al. The multifaceted roles of extracellular vesicles in osteonecrosis of the femoral head［J］. J Orthop Translat， 2025， 52： 70-84. doi:10.1016/j.jot.2025.03.009 doi: 10.1016/j.jot.2025.03.009
[6]	YU H， LIU P， ZUO W， et al. Decreased angiogenic and increased apoptotic activities of bone microvascular endothelial cells in patients with glucocorticoid-induced osteonecrosis of the femoral head［J］. BMC Musculoskelet Disord， 2020， 21（1）： 277. doi:10.1186/s12891-020-03225-1 doi: 10.1186/s12891-020-03225-1
[7]	HASAN S S， JOHN D， RUDNICKI M， et al. Obesity drives depot-specific vascular remodeling in male white adipose tissue［J］. Nat Commun， 2025， 16（1）： 5392. doi:10.1038/s41467-025-60910-2 doi: 10.1038/s41467-025-60910-2
[8]	DUAN P， YU Y L， CHENG Y N， et al. Exosomal miR-1a-3p derived from glucocorticoid-stimulated M1 macrophages promotes the adipogenic differentiation of BMSCs in glucocorticoid-associated osteonecrosis of the femoral head by targeting Cebpz［J］. J Nanobiotechnology， 2024， 22（1）： 648. doi:10.1186/s12951-024-02923-5 doi: 10.1186/s12951-024-02923-5
[9]	DUAN D Y， TANG J， TIAN H T， et al. Adipocyte-secreted microvesicle-derived miR-148a regulates adipogenic and osteogenic differentiation by targeting Wnt5a/Ror2 pathway［J］. Life Sci， 2021， 278： 119548. doi:10.1016/j.lfs.2021.119548 doi: 10.1016/j.lfs.2021.119548
[10]	郭民康，张健. 基于超高效液相色谱-串联质谱的股骨头坏死组织外泌体脂质代谢组学分析［J］. 色谱， 2022， 40（2）： 123-129.
[11]	BIAN X， JIN L， WANG Y， et al. Riboflavin deficiency reduces bone mineral density in rats by compromising osteoblast function［J］. J Nutr Biochem， 2023， 122： 109453. doi:10.1016/j.jnutbio.2023.109453 doi: 10.1016/j.jnutbio.2023.109453
[12]	ZHU T， JIANG M， ZHANG M， et al. Biofunctionalized composite scaffold to potentiate osteoconduction， angiogenesis， and favorable metabolic microenvironment for osteonecrosis therapy［J］. Bioact Mater， 2021， 9： 446-460. doi:10.1016/j.bioactmat.2021.08.005 doi: 10.1016/j.bioactmat.2021.08.005
[13]	YANG W， ZHU W， YANG Y， et al. Exosomal miR-100-5p inhibits osteogenesis of hBMSCs and angiogenesis of HUVECs by suppressing the BMPR2/Smad1/5/9 signalling pathway［J］. Stem Cell Res Ther， 2021， 12（1）： 390. doi:10.1186/s13287-021-02438-y doi: 10.1186/s13287-021-02438-y
[14]	LAN X， MA H， XIONG Y， et al. Bone marrow mesenchymal stem cells-derived exosomes mediate nuclear receptor coactivator-3 expression in osteoblasts by delivering miR-532-5p to influence osteonecrosis of the femoral head development［J］. Cell Biol Int， 2022， 46（12）： 2185-2197. doi:10.1002/cbin.11902 doi: 10.1002/cbin.11902
[15]	LI S， KONG Z， MA B， et al. Low miR-182-5p Expressing Extracellular Vesicles Derived From Human Bone Marrow Stromal Cells of Subjects With Steroid-Induced Osteonecrosis of the Femoral Head Aggravate Disease Progression［J］. J Bone Miner Res. 2023， 38（7）： 976-993. doi:10.1002/jbmr.4823 doi: 10.1002/jbmr.4823
[16]	ZHU W， GUO M， YANG W， et al. CD41-deficient exosomes from non-traumatic femoral head necrosis tissues impair osteogenic differentiation and migration of mesenchymal stem cells［J］. Cell Death Dis， 2020， 11（4）： 293. doi:10.1038/s41419-020-2496-y doi: 10.1038/s41419-020-2496-y
[17]	CHEN T， CHEN D， SU W， et al. Extracellular vesicles as vital players in drug delivery： A focus on clinical disease treatment［J］. Front Bioeng Biotechnol， 2025， 13： 1600227. doi:10.3389/fbioe.2025.1600227 doi: 10.3389/fbioe.2025.1600227
[18]	WU Z， JI C， LI H， et al. Elevated level of membrane microparticles in the disease of steroid-induced vascular osteonecrosis［J］. J Craniofac Surg， 2013， 24（4）： 1252-1256. doi:10.1097/scs.0b013e3182902dd3 doi: 10.1097/scs.0b013e3182902dd3
[19]	洪天添，刘望，黄嘉祺，等. LPS刺激稳定黏附于ICAM-1上的中性粒细胞形成胞外诱捕网依赖于整合素Mac-1和细胞骨架蛋白［J］. 生物医学工程学杂志， 2021， 38（5）： 903-910.
[20]	刘慧珍，卢晓南，柳歌，等. 肿节风总黄酮影响骨髓间充质干细胞及其外泌体促进巨核细胞分化的作用及机制［J］. 实用医学杂志， 2025， 41（11）： 1618-1626.
[21]	LI B， HUANG Q， LIN C， et al. Increased circulating CD31+/CD42b-EMPs in Perthes disease and inhibit HUVECs angiogenesis via endothelial dysfunction［J］. Life Sci， 2021， 265： 118749. doi:10.1016/j.lfs.2020.118749 doi: 10.1016/j.lfs.2020.118749
[22]	HUANG S L， XIN H Y， WANG X Y， et al. Recent Advances on the Molecular Mechanism and Clinical Trials of Venous Thromboembolism［J］. J Inflamm Res， 2023， 16： 6167-6178. doi:10.2147/jir.s439205 doi: 10.2147/jir.s439205
[23]	REN S， WANG C， GUO S. Review of the Role of Mesenchymal Stem Cells and Exosomes Derived from Mesenchymal Stem Cells in the Treatment of Orthopedic Disease［J］. Med Sci Monit， 2022， 28： e935937. doi:10.12659/msm.935937 doi: 10.12659/msm.935937
[24]	LI L， WANG Y， YU X， et al. Bone marrow mesenchymal stem cell-derived exosomes promote plasminogen activator inhibitor 1 expression in vascular cells in the local microenvironment during rabbit osteonecrosis of the femoral head［J］. Stem Cell Res Ther， 2020， 11（1）： 480. doi:10.1186/s13287-020-01991-2 doi: 10.1186/s13287-020-01991-2
[25]	WA Q， LUO Y， TANG Y， et al. Mesoporous bioactive glass-enhanced MSC-derived exosomes promote bone regeneration and immunomodulation in vitro and in vivo［J］. J Orthop Translat， 2024， 49： 264-282. doi:10.1016/j.jot.2024.09.009 doi: 10.1016/j.jot.2024.09.009
[26]	YUAN N， ZHANG W， YANG W， et al. Exosomes derived from M2 macrophages prevent steroid-induced osteonecrosis of the femoral head by modulating inflammation， promoting bone formation and inhibiting bone resorption［J］. J Orthop Surg Res， 2024， 19（1）： 243. doi:10.1186/s13018-024-04711-1 doi: 10.1186/s13018-024-04711-1
[27]	CHEN S， LIU J， ZHANG N， et al. Exploring of exosomes in pathogenesis， diagnosis and therapeutic of osteonecrosis of the femoral head： The mechanisms and signaling pathways［J］. Biomed Mater， 2024， 19（5）. doi:10.1088/1748-605x/ad6dc6 doi: 10.1088/1748-605x/ad6dc6
[28]	CHEN C， FU L， LUO Y， et al. Engineered Exosome-Functionalized Extracellular Matrix-Mimicking Hydrogel for Promoting Bone Repair in Glucocorticoid-Induced Osteonecrosis of the Femoral Head［J］. ACS Appl Mater Interfaces， 2023， 15（24）： 28891-28906. doi:10.1021/acsami.3c01539 doi: 10.1021/acsami.3c01539
[29]	XU H J， LIAO W， LIU X Z， et al. Down-regulation of exosomal microRNA-224-3p derived from bone marrow-derived mesenchymal stem cells potentiates angiogenesis in traumatic osteonecrosis of the femoral head［J］. FASEB J， 2019， 33（7）： 8055-8068. doi:10.1096/fj.201801618rrr doi: 10.1096/fj.201801618rrr
[30]	SHAW P， DWIVEDI S K D， BHATTACHARYA R， et al. VEGF signaling： Role in angiogenesis and beyond［J］. Biochim Biophys Acta Rev Cancer， 2024， 1879（2）： 189079. doi:10.1016/j.bbcan.2024.189079 doi: 10.1016/j.bbcan.2024.189079
[31]	YUAN N， GE Z， JI W， et al. Exosomes Secreted from Hypoxia-Preconditioned Mesenchymal Stem Cells Prevent Steroid-Induced Osteonecrosis of the Femoral Head by Promoting Angiogenesis in Rats［J］. Biomed Res Int， 2021， 2021： 6655225. doi:10.1155/2021/6655225 doi: 10.1155/2021/6655225
[32]	TANG J， WANG X， LIN X， Wu C. Mesenchymal stem cell-derived extracellular vesicles： A regulator and carrier for targeting bone-related diseases［J］. Cell Death Discov， 2024， 10（1）： 212. doi:10.1038/s41420-024-01973-w doi: 10.1038/s41420-024-01973-w
[33]	ZHANG Q， LI T， LI Z， et al. Autocrine Activity of Extracellular Vesicles Induced by Icariin and Its Effectiveness in Glucocorticoid-Induced Injury of Bone Microvascular Endothelial Cells［J］. Cells， 2022， 11（12）： 1921. doi:10.3390/cells11121921 doi: 10.3390/cells11121921
[34]	LOU P， ZHOU G， WEI B， et al. Sclerotic zone in femoral head necrosis： From pathophysiology to therapeutic implications［J］. Efort Open Rev， 2023， 8（6）： 451-458. doi:10.1530/eor-22-0092 doi: 10.1530/eor-22-0092
[35]	HANETSEDER D， LEVSTEK T， TEUSCHL Woller A H， et al. Engineering of extracellular matrix from human iPSC-mesenchymal progenitors to enhance osteogenic capacity of human bone marrow stromal cells independent of their age［J］. Front Bioeng Biotechnol， 2023， 11： 1214019. doi:10.3389/fbioe.2023.1214019 doi: 10.3389/fbioe.2023.1214019
[36]	KOMORI T. Regulation of Skeletal Development and Maintenance by Runx2 and Sp7［J］. Int J Mol Sci， 2024， 25（18）： 10102. doi:10.3390/ijms251810102 doi: 10.3390/ijms251810102
[37]	FANG S， HE T， JIANG J， et al. Osteogenic Effect of tsRNA-10277-Loaded Exosome Derived from Bone Mesenchymal Stem Cells on Steroid-Induced Osteonecrosis of the Femoral Head［J］. Drug Des Devel Ther， 2020， 14： 4579-4591. doi:10.2147/dddt.s258024 doi: 10.2147/dddt.s258024
[38]	FANG S， LIU Z， WU S， et al. Pro-angiognetic and pro-osteogenic effects of human umbilical cord mesenchymal stem cell-derived exosomal miR-21-5p in osteonecrosis of the femoral head［J］. Cell Death Discov， 2022， 8（1）： 226. doi:10.1038/s41420-022-00971-0 doi: 10.1038/s41420-022-00971-0
[39]	HUANG S， LI Y， WU P， et al. microRNA-148a-3p in extracellular vesicles derived from bone marrow mesenchymal stem cells suppresses SMURF1 to prevent osteonecrosis of femoral head［J］. J Cell Mol Med， 2020， 24（19）： 11512-11523. doi:10.1111/jcmm.15766 doi: 10.1111/jcmm.15766
[40]	谢志鸿，彭吾训. 骨髓间充质干细胞治疗股骨头坏死的研究进展［J］. 实用医学杂志， 2021， 37（1）： 20-24.
[41]	LI L， ZHAO S， LENG Z， et al. Pathological mechanisms and related markers of steroid-induced osteonecrosis of the femoral head［J］. Ann Med， 2024， 56（1）： 2416070. doi:10.1080/07853890.2024.2416070 doi: 10.1080/07853890.2024.2416070
[42]	王雨顺，郑鉴锐，罗玉鸿，等. 巨噬细胞介导的骨免疫在股骨头坏死中的作用及其机制研究［J］. 中国修复重建外科杂志， 2024， 38（1）： 119-124.
[43]	JIN S， MENG C， HE Y， et al. Curcumin prevents osteocyte apoptosis by inhibiting M1-type macrophage polarization in mice model of glucocorticoid-associated osteonecrosis of the femoral head［J］. J Orthop Res， 2020， 38（9）： 2020-2030. doi:10.1002/jor.24619 doi: 10.1002/jor.24619
[44]	LAN X， YU R， XU J， et al. Exosomes from chondrocytes overexpressing miR-214-3p facilitate M2 macrophage polarization and angiogenesis to relieve Legg Calvé-Perthes disease［J］. Cytokine， 2023， 168： 156233. doi:10.1016/j.cyto.2023.156233 doi: 10.1016/j.cyto.2023.156233
[45]	侯勇哲，张琴，赵霄晨，等. 间充质干细胞来源的胞外囊泡在急性肺损伤治疗中的研究进展［J］. 实用医学杂志， 2023， 39（3）： 390-394. doi:10.3969/j.issn.1006-5725.2023.03.023 doi: 10.3969/j.issn.1006-5725.2023.03.023
[46]	LIU M， MARTIN A， ONI JK， et al. Towards Visualizing Early-stage Osteonecrosis using Intraoperative Imaging Modalities［J］. Comput Methods Biomech Biomed Eng Imaging Vis， 2023， 11（4）： 1234-1242. doi:10.1080/21681163.2022.2157329 doi: 10.1080/21681163.2022.2157329
[47]	FEUERRIEGEL G C， SUTTER R. Managing hardware-related metal artifacts in MRI： Current and evolving techniques［J］. Skeletal Radiol， 2024， 53（9）： 1737-1750. doi:10.1007/s00256-024-04624-4 doi: 10.1007/s00256-024-04624-4
[48]	QUAN H， REN C， HE Y， et al. Application of biomaterials in treating early osteonecrosis of the femoral head： Research progress and future perspectives［J］. Acta Biomater， 2023， 164： 15-73. doi:10.1016/j.actbio.2023.04.005 doi: 10.1016/j.actbio.2023.04.005
[49]	SUNG S E， LIM J H， KANG K K， et al. Proteomic profiling of extracellular vesicles derived from human serum for the discovery of biomarkers in Avascular necrosis［J］. Clin Proteomics， 2024， 21（1）： 39. doi:10.1186/s12014-024-09489-2 doi: 10.1186/s12014-024-09489-2
[50]	ZHANG M， CHEN D， ZHANG F， et al. Serum exosomal hsa-miR-135b-5p serves as a potential diagnostic biomarker in steroid-induced osteonecrosis of femoral head［J］. Am J Transl Res， 2020， 12（5）： 2136-2154.
[51]	CHEN D， ZHANG G， LI Y， et al. Up-regulation of urinary exosomal hsa-microRNA-200b-3p and hsa-microRNA-206 in patients of steroid-induced osteonecrosis of femoral head［J］. Am J Transl Res， 2021， 13（7）： 7574-7590.
[52]	YANG G， ZHAO G， ZHANG J， et al. Global urinary metabolic profiling of the osteonecrosis of the femoral head based on UPLC-QTOF/MS［J］. Metabolomics， 2019， 15（3）： 26. doi:10.1007/s11306-019-1491-8 doi: 10.1007/s11306-019-1491-8

Research progress on the treatment of femoral skull necrosis by extracellular vesicles from bone marrow mesenchymal stem cells

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 1

References 52

Related Articles 13

Recommended Articles

Metrics

Comments

[1]	Jingwen LAI,Yuchuan ZHAO,Zhuhua WU,Xunxun CHEN,Kehao PENG,Yuhui CHEN,Ran WEI,Xiaoyu LAI,Jingyu. WANG. Research advances and challenges in tuberculosis⁃associated extracellular vesicle biomarkers [J]. The Journal of Practical Medicine, 2025, 41(14): 2278-2284.
[2]	Huizhen LIU,Xiaonan LU,Ge LIU,Guanqing CAI,Pingan LI,Yingjian ZENG,Guangbin SHANG. The effects and mechanism of total flavonoids of Sarcandra glabra in modulating bone marrow mesenchymal stem cells and their exosomes to promote megakaryocyte differentiation [J]. The Journal of Practical Medicine, 2025, 41(11): 1618-1626.
[3]	CHEN Xia, WU Xinxin, LIU Xingyou, CHEN Xinhao, HUANG Yinxia, XIAO Zhiyuan, HE Jigang. . Overexpressed NKx2.5 genes in mesenchymal stem cells improve myocardial function in patients with myo⁃ cardial infarction via enhancing SDF⁃1/CXCR4⁃axis homing [J]. The Journal of Practical Medicine, 2023, 39(6): 660-666.
[4]	HOU Yongzhe, ZHANG Qin, ZHAO Xiaochen, HE Miao, YU Lingling, BAI Hai, WU Tao.. Research progress of extracellular vesicles derived from mesenchymal stem cells in treatment of acute lung injury [J]. The Journal of Practical Medicine, 2023, 39(3): 390-394.
[5]	Changsong MA,Shuai HUANG,Qingde WA,Weizhi CHEN,Yang WANG,Xitao LINGHU,Yubo. TANG. Mechanism of ginkgolide B antagonizing vascular endothelial injury by inhibiting endoplasmic reticulum stress [J]. The Journal of Practical Medicine, 2023, 39(24): 3175-3181.
[6]	LÜ Yajun, REN Lizhong, LI Jun, ZHANG Hai⁃ jing, ZHANG Zhikun. Second . Effects of core decompression combined with collagen⁃based bone repair materials and VEGF on vascular repair and microcirculation in rabbit femoral head necrosis [J]. The Journal of Practical Medicine, 2022, 38(23): 2927-2932.
[7]	HONG Jiaying, ZHANG Tao.. Research progress of biodegradable Mg ⁃ based metals as bone infection repair material [J]. The Journal of Practical Medicine, 2022, 38(12): 1449-1455.
[8]	LIU Xiaoli, ZHOU Lin, HAN Chongxu. Extracellular vesicle，a new marker for diagnosis and prognosis of myeloma [J]. The Journal of Practical Medicine, 2021, 37(8): 1084-1092.
[9]	LIAN Xuehui , XIAO Hongli, DENG Jiang, HAN Ziji, QI Weilin.. Effect of local transplantation of hBDNF⁃BMSCs on the repair of spinal cord injury in rats [J]. The Journal of Practical Medicine, 2021, 37(20): 2590-2596.
[10]	WANG Ti′ er, SHI Mingxia. . Research advance in paracrine role of mesenchymal stem cells [J]. The Journal of Practical Medicine, 2021, 37(13): 1651-1654.
[11]	WANG Bo, GUO Huili. . Analysis of clinical effect and safety of Yunke combined with Gugutou Huaisiyu capsule in the treatment of early non⁃traumatic femoral head necrosis [J]. The Journal of Practical Medicine, 2021, 37(10): 1328-1331.
[12]	XIE Zhihong, PENG Wuxun. Research progress of bone marrow mesenchymal stem in the treatment of osteonecrosis of femoral head [J]. The Journal of Practical Medicine, 2021, 37(1): 20-24.
[13]	CHEN Binwei, LIU Shengyao, HUANG Shuai, WANG Bin, CHEN Yuanhong. Simvastatin promotes the osteogenic differentiation of BMSCs induced by mechanical stretch via Wnt/β ⁃ catenin signaling pathway [J]. The Journal of Practical Medicine, 2021, 37(1): 41-45.