实用医学杂志 ›› 2025, Vol. 41 ›› Issue (23): 3631-3637.doi: 10.3969/j.issn.1006-5725.2025.23.001
• 专题笔谈 •
收稿日期:2025-09-10
出版日期:2025-12-10
发布日期:2025-12-18
通讯作者:
张旭升
E-mail:2161447918@qq.com
基金资助:
Aiqiang LI1,Ning ZHAO1,Xusheng ZHANG2(
),Haiping. LIU1
Received:2025-09-10
Online:2025-12-10
Published:2025-12-18
Contact:
Xusheng ZHANG
E-mail:2161447918@qq.com
摘要:
股骨头坏死(osteonecrosis of the femoral head,ONFH)是一种致残性骨科疾病,以进行性股骨头塌陷伴骨小梁、关节软骨结构破坏为病理特征,导致髋关节疼痛及进行性功能障碍。骨髓间充质干细胞来源细胞外囊泡(BMSC-derived exosomes,BMSC-EVs)在组织修复和再生方面有良好的前景,免疫原性和致瘤性较低,影响成骨、成血管和免疫调节。本文综述了BMSC-EVs在ONFH中的治疗效果及其潜在机制,为ONFH的治疗提供理论依据。
中图分类号:
李爱强,赵宁,张旭升,柳海平. 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[J]. 实用医学杂志, 2025, 41(23): 3631-3637.
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.
| [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 |
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