Application and progress of exosomes derived from mesenchymal stem cells in bone defect regeneration

doi:10.3760/cma.j.issn.1007-1245.2023.03.003

Abstract

Abstract:

Exosomes are extracellular vesicles derived from paracrine cells. Because exosomes contain a variety of bioactive factors, they play an important role in cell-cell communication and inducing cell differentiation. Exosomes derived from mesenchymal stem cells can promote the bone defect regeneration by affecting the proliferation of bone tissue cells, inducing the osteogenesis through signaling pathway regulation, and reducing the immune inflammatory response. In recent years, researchers have paid more attention to the relationship between exosomes and bone defect regeneration. This paper reviews the research progress in this field.

Key words:

Bone defect, Bone regeneration, Mesenchymal stem cells, Exosomes

摘要：

外泌体是来自细胞旁分泌的一种细胞外囊泡，因其含有多种生物活性因子，在细胞间通讯、诱导细胞分化中起重要作用。间充质干细胞来源的外泌体能够影响骨组织细胞增殖、通过信号通路调控诱导成骨、减少免疫炎性反应来促进骨缺损再生。近年来，外泌体与骨缺损再生之间的关系引起研究者的注意。本文对此方面的研究进展进行综述。

关键词:

骨缺损, 骨再生, 间充质干细胞, 外泌体

Zhang Zhiwei, Zhou Nan, Li Mengqi, Zhang Kai, Li Peng.

Application and progress of exosomes derived from mesenchymal stem cells in bone defect regeneration [J]. International Medicine and Health Guidance News, 2023, 29(3): 306-310.

张志伟周楠李孟奇张锴李朋.

间充质干细胞来源外泌体在骨缺损再生中的应用与进展 [J]. 国际医药卫生导报, 2023, 29(3): 306-310.

References

[1] 刘维辉,何清柳,穆鑫,陈国锋,陈俊毅,李毅宁.膀胱癌来源外泌体携带程序性死亡配体1和共刺激分子B7-H4的表达及初步鉴定[J].哈尔滨医药,2021,41(6):69-71. DOI:10.3969/j.issn.1001-8131.2021.06.033.
[2] Mauffrey C, Barlow BT, Smith W. Management of segmental bone defects[J]. J Am Acad Orthop Surg,2015,23(3):143-153. DOI:10.5435/JAAOS-D-14-00018.
[3] Keating JF, Simpson AH, Robinson CM. The management of fractures with bone loss[J].J Bone Joint Surg Br,2005,87(2):142-150. DOI:10.1302/0301-620x.87b2.15874.
[4] Sanders DW, Bhandari M, Guyatt G, et al. Critical-sized defect in the tibia: is it critical? Results from the SPRINT trial[J].J Orthop Trauma,2014,28(11):632-635. DOI:10.1097/BOT.0000000000000194.
[5] 秦宇星,任前贵,沈佩锋. 组织工程骨技术治疗骨缺损的优越性[J]. 中国组织工程研究,2020,24(24):3877-3882. DOI:10.3969/j.issn.2095-4344.2705.
[6] 戚晓阳,邱旭升,施鸿飞,等. 大段骨缺损的治疗进展[J]. 实用骨科杂志,2017,23(8):715-719. DOI:10.13795/j.cnki.sgkz.2017.08.010.
[7] 邢浩,张永红,王栋. 长骨大段骨缺损修复方法的优势与不足[J]. 中国组织工程研究,2021,25(3):426-430.
[8] Sohn HS, Oh JK. Review of bone graft and bone substitutes with an emphasis on fracture surgeries[J].Biomater Res,2019,23:9. DOI:10.1186/s40824-019-0157-y.
[9] 陈欣,张春林. 组织工程骨修复骨缺损的研究进展及临床应用[J]. 中国组织工程研究与临床康复,2010,14(24):4486-4490. DOI:10.3969/j.issn.1673-8225.2010.24.027.
[10] Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors[J].Cell,2006,126(4):663-676. DOI:10.1016/j.cell.2006.07.024.
[11] Kfoury Y, Scadden DT. Mesenchymal cell contributions to the stem cell niche[J].Cell Stem Cell,2015,16(3):239-253. DOI:10.1016/j.stem.2015.02.019.
[12] Mazini L, Rochette L, Amine M, et al. Regenerative capacity of adipose derived stem cells (ADSCs), comparison with mesenchymal stem cells (MSCs)[J].Int J Mol Sci,2019,20(10):2523. DOI:10.3390/ijms20102523.
[13] Kanczler JM, Ginty PJ, Barry JJ, et al. The effect of mesenchymal populations and vascular endothelial growth factor delivered from biodegradable polymer scaffolds on bone formation[J].Biomaterials,2008,29(12):1892-1900. DOI:10.1016/j.biomaterials.2007.12.031.
[14] Han C, Sun X, Liu L, et al. Exosomes and their therapeutic potentials of stem cells[J].Stem Cells Int,2016,2016:7653489. DOI:10.1155/2016/7653489.
[15] Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators[J].J Cell Biochem,2006,98(5):1076-1084. DOI:10.1002/jcb.20886.
[16] Lai RC, Yeo RW, Lim SK. Mesenchymal stem cell exosomes[J].Semin Cell Dev Biol,2015,40:82-88. DOI:10.1016/j.semcdb.2015.03.001.
[17] Trams EG, Lauter CJ, Salem N, et al. Exfoliation of membrane ecto-enzymes in the form of micro-vesicles[J].Biochim Biophys Acta,1981,645(1):63-70. DOI:10.1016/0005-2736(81)90512-5.
[18] 卢婉,杨人强,王伶.外泌体的研究进展[J].生命的化学,2013,33(4):438-442.
[19] Trajkovic K, Hsu C, Chiantia S, et al. Ceramide triggers budding of exosome vesicles into multivesicular endosomes[J].Science,2008,319(5867):1244-1247. DOI:10.1126/science.1153124.
[20] Pegtel DM, Gould SJ. Exosomes[J].Annu Rev Biochem,2019,88:487-514. DOI:10.1146/annurev- biochem-013118-111902.
[21] Morelli AE, Larregina AT, Shufesky WJ, et al. Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells[J].Blood,2004,104(10):3257-3266. DOI:10.1182/blood-2004-03-0824.
[22] Caby MP, Lankar D, Vincendeau-Scherrer C, et al. Exosomal-like vesicles are present in human blood plasma[J].Int Immunol,2005,17(7):879-887. DOI:10.1093/intimm/dxh267.
[23] Skriner K, Adolph K, Jungblut PR, et al. Association of citrullinated proteins with synovial exosomes[J].Arthritis Rheum,2006,54(12):3809-3814. DOI:10.1002/art.22276.
[24] Ogawa Y, Miura Y, Harazono A, et al. Proteomic analysis of two types of exosomes in human whole saliva[J].Biol Pharm Bull,2011,34(1):13-23. DOI:10.1248/bpb.34.13.
[25] Heldring N, Mäger I, Wood MJ, et al. Therapeutic potential of multipotent mesenchymal stromal cells and their extracellular vesicles[J].Hum Gene Ther,2015,26(8):506-517. DOI:10.1089/hum.2015.072.
[26] Kosaka N, Iguchi H, Yoshioka Y, et al. Secretory mechanisms and intercellular transfer of microRNAs in living cells[J].J Biol Chem,2010,285(23):17442-17452. DOI:10.1074/jbc.M110.107821.
[27] Record M, Carayon K, Poirot M, et al. Exosomes as new vesicular lipid transporters involved in cell-cell communication and various pathophysiologies[J].Biochim Biophys Acta,2014,1841(1):108-120. DOI:10.1016/j.bbalip.2013.10.004.
[28] Orlic D, Kajstura J, Chimenti S, et al. Bone marrow stem cells regenerate infarcted myocardium[J].Pediatr Transplant,2003,7 Suppl 3:86-88. DOI:10.1034/j.1399-3046.7.s3.13.x.
[29] Yeo RW, Lai RC, Zhang B, et al. Mesenchymal stem cell: an efficient mass producer of exosomes for drug delivery[J].Adv Drug Deliv Rev,2013,65(3):336-341. DOI:10.1016/j.addr.2012.07.001.
[30] Timmers L, Lim SK, Arslan F, et al. Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium[J].Stem Cell Res,2007,1(2):129-137. DOI:10.1016/j.scr.2008.02.002.
[31] Liao W, Ning Y, Xu HJ, et al. BMSC-derived exosomes carrying microRNA-122-5p promote proliferation of osteoblasts in osteonecrosis of the femoral head[J].Clin Sci (Lond),2019,133(18):1955-1975. DOI:10.1042/CS20181064.
[32] Zhang B, Wang M, Gong A, et al. HucMSC-exosome mediated-wnt4 signaling is required for cutaneous wound healing[J].Stem Cells,2015,33(7):2158-2168. DOI:10.1002/stem.1771.
[33] Yang J, Chen Z, Pan D, et al. Umbilical cord-derived mesenchymal stem cell-derived exosomes combined pluronic F127 hydrogel promote chronic diabetic wound healing and complete skin regeneration[J].Int J Nanomedicine,2020,15:5911-5926. DOI:10.2147/IJN.S249129.
[34] Baulch JE, Acharya MM, Allen BD, et al. Cranial grafting of stem cell-derived microvesicles improves cognition and reduces neuropathology in the irradiated brain[J].Proc Natl Acad Sci U S A,2016,113(17):4836-4841. DOI:10.1073/pnas.1521668113.
[35] Zhang Y, Chopp M, Liu XS, et al. Exosomes derived from mesenchymal stromal cells promote axonal growth of cortical neurons[J].Mol Neurobiol,2017,54(4):2659-2673. DOI:10.1007/s12035-016-9851-0.
[36] Zhang J, Liu X, Li H, et al. Exosomes/tricalcium phosphate combination scaffolds can enhance bone regeneration by activating the PI3K/Akt signaling pathway[J].Stem Cell Res Ther,2016,7(1):136. DOI:10.1186/s13287-016-0391-3.
[37] Qi X, Zhang J, Yuan H, et al. Exosomes secreted by human-induced pluripotent stem cell-derived mesenchymal stem cells repair critical-sized bone defects through enhanced angiogenesis and osteogenesis in osteoporotic rats[J].Int J Biol Sci,2016,12(7):836-849. DOI:10.7150/ijbs.14809.
[38] Nong K, Wang W, Niu X, et al. Hepatoprotective effect of exosomes from human-induced pluripotent stem cell-derived mesenchymal stromal cells against hepatic ischemia-reperfusion injury in rats[J].Cytotherapy,2016,18(12):1548-1559. DOI:10.1016/j.jcyt.2016.08.002.
[39] Tan CY, Lai RC, Wong W, et al. Mesenchymal stem cell-derived exosomes promote hepatic regeneration in drug-induced liver injury models[J].Stem Cell Res Ther,2014,5(3):76. DOI:10.1186/scrt465.
[40] Zhang L, Jiao G, Ren S, et al. Exosomes from bone marrow mesenchymal stem cells enhance fracture healing through the promotion of osteogenesis and angiogenesis in a rat model of nonunion[J].Stem Cell Res Ther,2020,11(1):38. DOI:10.1186/s13287-020-1562-9.
[41] Cazzoli R, Buttitta F, Di Nicola M, et al. microRNAs derived from circulating exosomes as noninvasive biomarkers for screening and diagnosing lung cancer[J].J Thorac Oncol,2013,8(9):1156-1162. DOI:10.1097/JTO.0b013e318299ac32.
[42] Osugi M, Katagiri W, Yoshimi R, et al. Conditioned media from mesenchymal stem cells enhanced bone regeneration in rat calvarial bone defects[J].Tissue Eng Part A,2012,18(13-14):1479-1489. DOI:10.1089/ten.TEA.2011.0325.
[43] Furuta T, Miyaki S, Ishitobi H, et al. Mesenchymal stem cell-derived exosomes promote fracture healing in a mouse model[J].Stem Cells Transl Med,2016,5(12):1620-1630. DOI:10.5966/sctm.2015-0285.
[44] Qin Y, Wang L, Gao Z, et al. Bone marrow stromal/stem cell-derived extracellular vesicles regulate osteoblast activity and differentiation in vitro and promote bone regeneration in vivo[J].Sci Rep,2016,6:21961. DOI:10.1038/srep21961.
[45] Lin Z, Xiong Y, Meng W, et al. Exosomal PD-L1 induces osteogenic differentiation and promotes fracture healing by acting as an immunosuppressant[J].Bioact Mater,2021,13:300-311. DOI:10.1016/j.bioactmat.2021.10.042.
[46] Kim HS, Choi DY, Yun SJ, et al. Proteomic analysis of microvesicles derived from human mesenchymal stem cells[J].J Proteome Res,2012,11(2):839-849. DOI:10.1021/pr200682z.
[47] Shi Y, Kang X, Wang Y, et al. Exosomes derived from bone marrow stromal cells (BMSCs) enhance tendon-bone healing by regulating macrophage polarization[J].Med Sci Monit,2020,26:e923328. DOI:10.12659/MSM.923328.