切换至 "中华医学电子期刊资源库"
高级检索
中华细胞与干细胞杂志(电子版)

中华细胞与干细胞杂志(电子版) ›› 2022, Vol. 12 ›› Issue (05) : 309 -313. doi: 10.3877/cma.j.issn.2095-1221.2022.05.008

综述

间充质干细胞源性外泌体对子痫前期滋养层细胞生物学行为影响的研究进展
何豆豆1, 孙晓彤2,†(), 曲涛3, 李忠媛1, 杨雪萍1   
  1. 1. 730000　兰州，甘肃中医药大学第一临床医学院
    2. 730000　兰州，甘肃省人民医院产科
    3. 730000　兰州，甘肃省人民医院生物转化所实验室
  • 收稿日期:2022-09-09 出版日期:2022-10-01
  • 通信作者: 孙晓彤
  • 基金资助:
    国家自然科学基金地区科学基金项目(32060172); 甘肃省科技计划项目（创新基地和人才计划）(21JR7RA608); 甘肃省青年科技基金(20JR10RA416)

Research progress on the effects of mesenchymal stem cell-derived exosomes on the biological behaviour of preeclamptic trophoblast cells

Doudou He1, Xiaotong Sun2,†(), Tao Qu3, Zhongyuan Li1, Xueping Yang1   

  1. 1. The First Clinical Medical College of Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China
  • Received:2022-09-09 Published:2022-10-01
  • Corresponding author: Xiaotong Sun
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

何豆豆, 孙晓彤, 曲涛, 李忠媛, 杨雪萍. 间充质干细胞源性外泌体对子痫前期滋养层细胞生物学行为影响的研究进展[J]. 中华细胞与干细胞杂志(电子版), 2022, 12(05): 309-313.

Doudou He, Xiaotong Sun, Tao Qu, Zhongyuan Li, Xueping Yang. Research progress on the effects of mesenchymal stem cell-derived exosomes on the biological behaviour of preeclamptic trophoblast cells[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2022, 12(05): 309-313.

子痫前期（PE）是一种严重影响孕产妇围产结局的妊娠中晚期特有并发症，其具体发病机制至今仍不明确，且目前尚无有效的治疗手段。外泌体作为间充质干细胞（MSCs）旁分泌作用的主要方式，在细胞间的信息交流中扮演重要角色，同时发现外泌体内携带的如微小RNA （miRNA）等小分子物质参与靶向细胞的多种生理病理过程。近年来相关研究发现不同来源MSCs的外泌体能够通过改善滋养层细胞功能为治疗PE患者提供潜在的治疗手段。随着研究的不断深入，不同来源MSCs及其外泌体将在PE患者的靶向药物治疗方面发挥巨大的潜力，可降低PE患者不良围产结局发生率及保障围产期母婴安全。本文将通过阐述不同来源MSCs的基本特点，分析其外泌体在PE滋养层细胞中的治疗作用，为临床治疗PE患者提供新的视角和思路。

关键词: 间充质干细胞, 子痫前期, 旁分泌, 外泌体, miRNA

Preeclampsia (PE) is a unique complication in the second and third trimesters of pregnancy that seriously affects the perinatal outcome of pregnant women. Its specific pathogenesis is still unclear, and there is currently no effective treatment. As the main mode of the paracrine effect of mesenchymal stem cells (MSCs) , exosomes play an essential role in the communication of information between cells. Exosomes that carry small molecules such as micorRNAs have also been found to be involved in a physiological and pathological process. In recent years, related studies have found that exosomes from different sources of MSCs can provide a potential therapeutic method for treating PE by improving the function of trophoblast cells. It is believed that with the continuous deepening of research, MSCs from different sources and their exosomes will play amassive potential in the targeted drug therapy of patients with PE, reducing the incidence of adverse perinatal outcomes and ensuring the safety of mothers and babies. This article will describe the essential characteristics of MSCs from different sources and analyze the therapeutic effect of exosomes in PE trophoblast cells to provide new perspectives and ideas for the clinical treatment of PE.

Key words: Mesenchymal stem cells, Preeclampsia, Paracrine, Exosomes, miRNA
1
Aneman I, Pienaar D, Suvakov S, et al. Mechanisms of key innate immune cells in early-and late-onset preeclampsia[J]. Front Immunol, 2020, 11:1864. doi:10.3389/fimmu.2020.01864.
2
Suvakov S, Richards C, Nikolic V, et al. Emerging therapeutic totential of mesenchymal stem/stromal cells in preeclampsia[J]. Curr Hypertens Rep, 2020, 22(5):37. doi: 10.1007/s11906-020-1034-8.
3
史昊然, 赵茵. 间充质干细胞来源的外泌体在子痫前期中的实验研究进展[J]. 中华围产医学杂志, 2022, 25(2):154-157.
4
白佳萌,刘光伟,谢露,等.间充质干细胞及其外泌体在肝再生领域的应用[J].中国组织工程研究, 2022, 26(19):3071-3077.
5
Grimes S, Bombay K, Lanes A, et al. Potential biological therapies for severe preeclampsia: a systematic review and meta-analysis[J]. BMC Pregnancy Childbirth, 2019, 19(1):163. doi: 10.1186/s12884-019-2268-9.
6
彭绪峰, 陈方. 间充质干细胞外泌体的免疫调节功能及其在自身免疫炎性疾病中的应用[J/CD]. 中华细胞与干细胞杂志（电子版）, 2020, 10(4):246-250.
7
沈志明, 袁磊, 卢毅, 等. 间充质干细胞外泌体在创伤修复再生中作用的研究进展[J]. 中华创伤杂志, 2022, 38(2):182-186.
8
付长秀, 孙建伟, 张芸, 等. 间充质干细胞外泌体在眼部疾病中的研究进展[J].中国免疫学杂志, 2021, 37(18):2295-2299.
9
张雨诗, 曹莉旻, 文婷婷, 等. 间充质干细胞外泌体对肺部疾病的治疗及研究进展[J]. 国际呼吸杂志, 2022, 42(8):630-635.
10
Gupta PK, Das AK, Chullikana A, et al. Mesenchymal stem cells for cartilage repair in osteoarthritis[J]. Stem Cell Res Ther, 2012, 3(4):25.doi:10.1186/scrt116.
11
Barry F. MSC therapy for osteoarthritis: an unfinished story[J]. J Orthop Res, 2019, 37(6):1229-1235.
12
Volarevic V, Markovic BS, Gazdic M, et al. Ethical and safety issues of stem cell-based therapy[J]. Int J Med Sci, 2018, 15(1):36-45.
13
Ferreira JR, Teixeira GQ, Santos SG, et al. Mesenchymal stromal cell secretome: influencing therapeutic potential by cellular pre-conditioning[J]. Front Immunol, 2018, 9:2837. doi: 10.3389/fimmu.2018.02837.
14
Harrell CR, Fellabaum C, Jovicic N, et al. Molecular mechanisms responsible for therapeutic potential of mesenchymal stem cell-derived secretome[J]. Cells, 2019, 8(5):467. doi: 10.3390/cells8050467.
15
Li JJ, Hosseini-Beheshti E, Grau GE, et al. Stem cell-derived extracellular vesicles for treating joint injury and osteoarthritis[J]. Nanomaterials(Basel), 2019, 9(2):261. doi: 10.3390/nano9020261.
16
Caplan H, Olson SD, Kumar A, et al. Mesenchymal stromal cell therapeutic delivery: translational challenges to clinical application[J]. Front Immunol, 2019, 10:1645. doi: 10.3389/fimmu.2019.01645.
17
Zhu X, Badawi M, Pomeroy S, et al. Comprehensive toxicity and immunogenicity studies reveal minimal effects in mice following sustained dosing of extracellular vesicles derived from HEK293T cells[J]. J Extracell Vesicles, 2017, 6(1):1324730. doi:10.1080/20013078.2017.1324730.
18
Konečná B, Tóthová Ľ, Repiská G. Exosomes-associated DNA-new marker in pregnancy complications?[J]. Int J Mol Sci, 2019, 20(12):2890. doi:10.3390/ijms20122890.
19
van Niel G, D'Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles[J]. Nat Rev Mol Cell Biol, 2018, 19(4):213-228.
20
Pan Q, Wang Y, Lan Q, et al. Exosomes derived from mesenchymal stem cells ameliorate hypoxia/reoxygenation-injured ECs via transferring microRNA-126[J]. Stem Cells Int, 2019, 2019:2831756.doi:10.1155/2019/2831756.
21
Chen F, Chen X, Cai W, et al. Mesenchymal stem cell-derived exosomal long noncoding RNA MALAT1-201 regulated the proliferation, apoptosis and migration of trophoblast cells via targeting miR-141[J]. Ann Clin Lab Sci, 2022, 52(5):741-752.
22
Chen Y, Ding H, Wei M, et al. MSC-secreted exosomal H19 promotes trophoblast cell invasion and migration by downregulating let-7b and upregulating FOXO1[J]. Mol Ther Nucleic Acids, 2020, 19:1237-1249.
23
赵馨扬,谭季春.不同来源的间充质干细胞及其外泌体治疗早发性卵巢功能不全的作用及机制研究进展[J]. 中华生殖与避孕杂志, 2021, 41(7):661-667.
24
Ferreira LMR, Meissner TB, Tilburgs T, et al. HLA-G: at the interface of maternal-fetal tolerance[J]. Trends Immunol, 2017, 38(4):272-286.
25
Alshabibi MA, Khatlani T, Abomaray FM, et al. Human decidua basalis mesenchymal stem/stromal cells protect endothelial cell functions from oxidative stress induced by hydrogen peroxide and monocytes[J]. Stem Cell Res Ther, 2018, 9(1):275. doi: 10.1186/s13287-018-1021-z.
26
Kusuma GD, Abumaree MH, Perkins AV, et al. Reduced aldehyde dehydrogenase expression in preeclamptic decidual mesenchymal stem/stromal cells is restored by aldehyde dehydrogenase agonists[J]. Sci Rep, 2017, 7:42397. doi: 10.1038/srep42397.
27
Kamali Simsek N, Benian A, Sevgin K, et al. Microrna analysis of human decidua mesenchymal stromal cells from preeclampsia patients[J]. Placenta, 2021, 115:12-19.
28
Zhao G, Zhou X, Chen S, et al. Differential expression of microRNAs in decidua-derived mesenchymal stem cells from patients with preeclampsia[J]. J Biomed Sci, 2014, 21(1):81.doi: 10.1186/s12929-014-0081-3.
29
Xin G, Du J, Liu MY, et al. Upregulation of MiR-29b contributes to mesenchymal stem cell dysfunction in patients with severe pre-eclampsia[J]. Int J Clin Exp Pathol, 2017, 10(10):10243-10251.
30
Lei GQ, Wu ZY, Jiang WB, et al. Effect of CXCL12/CXCR4 on migration of decidua-derived mesenchymal stem cells from pregnancies with preeclampsia[J]. Am J Reprod Immunol, 2019, 82(5):e13180. doi: 10.1111/aji.13180.
31
Basmaeil YS, Algudiri D, Alenzi R, et al. HMOX1 is partly responsible for phenotypic and functional abnormalities in mesenchymal stem cells/stromal cells from placenta of preeclampsia (PE) patients[J]. Stem Cell Res Ther, 2020, 11(1):30. doi: 10.1186/s13287-020-1557-6.
32
Khatlani T, Algudiri D, Alenzi R, et al. Preconditioning by hydrogen peroxide enhances multiple properties of human decidua basalis mesenchymal stem/multipotent stromal cells[J]. Stem Cells Int, 2018, 2018:6480793. doi: 10.1155/2018/6480793.
33
Wu D, Liu Y, Liu X, et al. Heme oxygenase-1 gene modified human placental mesenchymal stem cells promote placental angiogenesis and spiral artery remodeling by improving the balance of angiogenic factors in vitro[J]. Placenta, 2020, 99:70-77.
34
Zheng S, Shi A, Hill S, et al. Decidual mesenchymal stem/stromal cell-derived extracellular vesicles ameliorate endothelial cell proliferation, inflammation, and oxidative stress in a cell culture model of preeclampsia[J]. Pregnancy Hypertens, 2020, 22:37-46.
35
Ridder A, Giorgione V, Khalil A, et al. Preeclampsia: the relationship between uterine artery blood flow and trophoblast function[J]. Int J Mol Sci, 2019, 20(13):3263.
36
Kannaiyan J, Muthukutty P, Iqbal MDT, et al. Villous chorion: a potential source for pluripotent-like stromal cells[J]. J Nat Sci Biol Med, 2017, 8(2):221-228.
37
Uder C, Brückner S, Winkler S, et al. Mammalian MSC from selected species: features and applications[J]. Cytometry A, 2018, 93(1):32-49.
38
Chu Y, Zhu C, Yue C, et al. Chorionic villus-derived mesenchymal stem cell-mediated autophagy promotes the proliferation and invasiveness of trophoblasts under hypoxia by activating the JAK2/STAT3 signalling pathway[J]. Cell Biosci, 2021, 11(1):182. doi: 10.1186/s13578-021-00681-7.
39
Abumaree MH, Alshehri NA, Almotery A, et al. Preconditioning human natural killer cells with chorionic villous mesenchymal stem cells stimulates their expression of inflammatory and anti-tumor molecules[J]. Stem Cell Res Ther, 2019, 10(1):50. doi: 10.1186/s13287-019-1153-9.
40
Li Y, Wang C, Xi HM, et al. Chorionic villus-derived mesenchymal stem cells induce E3 ligase TRIM72 expression and regulate cell behaviors through ubiquitination of p53 in trophoblasts[J]. FASEB J, 2021, 35(12):e22005. doi: 10.1096/fj.202100801R.
41
Umezawa A, Hasegawa A, Inoue M, et al. Amnion-derived cells as a reliable resource for next-generation regenerative medicine[J]. Placenta, 2019, 84:50-56.
42
薛玲玲,陈锦阳,庄盼,等.人羊膜上皮细胞和人羊膜间充质干细胞的研究进展[J/CD]. 中华细胞与干细胞杂志（电子版）, 2021, 11(3): 184-188.
43
Mac Donald ES, Barrett JG. The potential of mesenchymal stem cells to treat systemic inflammation in horses[J]. Front Vet Sci, 2020, 6:507. doi:10.3389/fvets.2019.00507.
44
Chu Y, Chen W, Peng W, et al. Amnion-derived mesenchymal stem cell exosomes-mediated autophagy promotes the survival of trophoblasts under hypoxia through mTOR pathway by the downregulation of EZH2[J]. Front Cell Dev Biol, 2020, 8:545852. doi: 10.3389/fcell.2020.545852.
45
Surico D, Bordino V, Cantaluppi V, et al. Preeclampsia and intrauterine growth restriction: Role of human umbilical cord mesenchymal stem cells-trophoblast cross-talk[J]. PLoS One, 2019, 14(6):e0218437.doi: 10.1371/journal.pone.0218437.
46
Liu H, Wang F, Zhang Y, et al. Exosomal microRNA-139-5p from mesenchymal stem cells accelerates trophoblast cell invasion and migration by motivation of the ERK/MMP-2 pathway via downregulation of protein tyrosine phosphatase[J]. J Obstet Gynaecol Res, 2020, 46(12):2561-2572.
47
Wang D, Na Q, Song GY, et al. Human umbilical cord mesenchymal stem cell-derived exosome-mediated transfer of microRNA-133b boosts trophoblast cell proliferation, migration and invasion in preeclampsia by restricting SGK1[J]. Cell Cycle, 2020, 19(15):1869-1883.
48
Huang Q, Gong M, Tan T, et al. Human umbilical cord mesenchymal stem cells-derived exosomal microRNA-18b-3p inhibits the occurrence of preeclampsia by targeting LEP[J]. Nanoscale Res Lett, 2021, 16(1):27. doi: 10.1186/s11671-021-03475-5.
49
Xiong ZH, Wei J, Lu MQ, et al. Protective effect of human umbilical cord mesenchymal stem cell exosomes on preserving the morphology and angiogenesis of placenta in rats with preeclampsia[J]. Biomed Pharmacother, 2018, 105:1240-1247.
50
Yang Z, Shan N, Deng Q, et al. Extracellular vesicle-derived microRNA-18b ameliorates preeclampsia by enhancing trophoblast proliferation and migration via Notch2/TIM3/mTORC1 axis[J]. J Cell Mol Med, 2021, 25(10):4583-4595.
51
Cui J, Chen X, Lin S, et al. MiR-101-containing extracellular vesicles bind to BRD4 and enhance proliferation and migration of trophoblasts in preeclampsiaJ]. Stem Cell Res Ther, 2020, 11(1):231.doi: 10.1186/s13287-020-01720-9.
52
Motawi TMK, Sabry D, Maurice NW, et al. Role of mesenchymal stem cells exosomes derived microRNAs; miR-136, miR-494 and miR-495 in pre-eclampsia diagnosis and evaluation[J]. Arch Biochem Biophys, 2018, 659:13-21.
53
Taglauer ES, Fernandez-Gonzalez A, Willis GR, et al. Antenatal mesenchymal stromal cell extracellular vesicle therapy prevents preeclamptic lung injury in mice[J]. Am J Respir Cell Mol Biol, 2022, 66(1):86-95.
54
Yang C, Lim W, Park J, et al. Anti-inflammatory effects of mesenchymal stem cell-derived exosomal microRNA-146a-5p and microRNA-548e-5p on human trophoblast cells[J]. Mol Hum Reprod, 2019, 25(11):755-771.
55
Peñailillo R, Acuña-Gallardo S, García F, et al. Mesenchymal stem cells-induced trophoblast invasion is reduced in patients with a previous history of preeclampsia[J]. Int J Mol Sci, 2022, 23(16):9071. doi: 10.3390/ijms23169071.
[1] 王岩, 马剑雄, 郎爽, 董本超, 田爱现, 李岩, 孙磊, 靳洪震, 卢斌, 王颖, 柏豪豪, 马信龙. 外泌体在骨质疏松症诊疗中应用的研究进展[J]. 中华关节外科杂志(电子版), 2023, 17(05): 673-678.
[2] 贺敬龙, 孙炜, 高明宏, 谢伟, 姜骆永, 何琦非, 岳家吉. 外泌体非编码RNA在骨关节炎发病机制中的研究进展[J]. 中华关节外科杂志(电子版), 2023, 17(04): 520-527.
[3] 代雯荣, 赵丽娟, 李智慧. 细胞外囊泡对胚胎着床影响的研究进展[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(05): 616-620.
[4] 高雷, 李芳, 巴雅力嘎, 李全, 巴特. 干细胞源性外泌体在创伤修复中免疫作用的研究进展[J]. 中华损伤与修复杂志(电子版), 2023, 18(04): 364-367.
[5] 唐英俊, 李华娟, 王赛妮, 徐旺, 刘峰, 李羲, 郝新宝, 黄华萍. 人脐带间充质干细胞治疗COPD小鼠及机制分析[J]. 中华肺部疾病杂志(电子版), 2023, 16(04): 476-480.
[6] 韦先梅, 韩毓, 蒋英彩. 敲减circSERPINE2通过靶向调控miR-34a-5p表达抑制滋养层细胞增殖、迁移和侵袭[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(04): 193-201.
[7] 李晔, 何洁, 胡锦秀, 王金祥, 田川, 潘杭, 陈梦蝶, 赵晓娟, 叶丽, 张敏, 潘兴华. 高活性间充质干细胞干预猕猴卵巢衰老的研究[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(04): 210-219.
[8] 龙慧玲, 林蜜, 邵婷. 三维球体间充质干细胞培养技术的研究进展及其应用[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(04): 229-234.
[9] 刘文慧, 吴涛, 张曦. 间充质干细胞联合血小板生成素受体激动剂在异基因造血干细胞移植后血小板恢复中的研究进展[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(04): 242-246.
[10] 王红敏, 谢云波, 王彦虎, 王福生. 间充质干细胞治疗新冠病毒感染的临床研究进展[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(04): 247-256.
[11] 王楚风, 蒋安. 原发性肝癌的分子诊断[J]. 中华肝脏外科手术学电子杂志, 2023, 12(05): 499-503.
[12] 杨蕴钊, 周诚, 石美涵, 赵静, 白雪源. 人羊水间充质干细胞对膜性肾病大鼠的治疗作用[J]. 中华肾病研究电子杂志, 2023, 12(04): 181-186.
[13] 宋艳琪, 任雪景, 王文娟, 韩秋霞, 续玥, 庄凯婷, 肖拓, 蔡广研. 间充质干细胞对顺铂诱导的小鼠急性肾损伤中细胞铁死亡的作用[J]. 中华肾病研究电子杂志, 2023, 12(04): 187-193.
[14] 孙昕, 程海波, 沈卫星. 基于全转录组学探讨仙连解毒方治疗Ⅲ期结直肠癌患者的疗效机制[J]. 中华消化病与影像杂志(电子版), 2023, 13(05): 277-283.
[15] 梁宇同, 丁旭, 马国慧, 黄艳红. 间充质干细胞在宫腔粘连治疗中的研究进展[J]. 中华临床医师杂志(电子版), 2023, 17(05): 596-599.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号