间充质干细胞在子宫内膜损伤修复中的机制研究进展

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摘要子宫内膜损伤是指因各种宫腔操作不当或次数过多所引起的子宫内膜基底层损伤，导致患者术后出现宫腔粘连、内膜薄化，并引发一系列包括经量过少、闭经、习惯性流产以及受孕困难等临床症状。尽管目前临床上针对子宫内膜损伤后修复的方法有很多，但对于中重度损伤后内膜再生的方法却十分有限，且各类方法均未取得较为满意的疗效。间充质干细胞因其独特的生物学特性，可分化为不同的细胞系，并分泌高水平蛋白，从而在子宫内膜修复领域拥有广泛的应用前景。本文针对近年来间充质干细胞在修复损伤后子宫内膜方面的相关性研究作一综述。

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收稿日期: 2022-01-13

基金资助: 广西壮族自治区自然科学基金面上项目(2017GXNSFAA198193)；广西重点研发计划项目(桂科AB18126056)；广西卫健委自筹经费科研课题(Z20190031)；广西医疗卫生适宜技术开发与推广应用项目(S2021033)；广西医疗卫生适宜技术开发与推广应用项目(S2021034)

通讯作者: 林忠（通讯作者），教授，E-mail：uters@126.com

作者简介: 刘姝岑(1993—)，女，硕士研究生

引用本文:

刘姝岑，朱雪红，宾力，等.. 间充质干细胞在子宫内膜损伤修复中的机制研究进展[J]. 江苏大学学报:医学版, 2023, 33(01): 84-92.

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http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2023/V33/I01/84

［1］Gilman AR, Dewar KM, Rhone SA, et al. Intrauterine adhesions following miscarriage: look and learn［J］. J Obstet Gynaecol Can, 2016, 38(5): 453-457.

［2］Chen L, Zhang H, Wang Q, et al. Reproductive outcomes in patients with intrauterine adhesions following hysteroscopic adhesiolysis: experience from the largest women′s hospital in China［J］. J Minim Invasive Gynecol, 2017, 24(2): 299-304.

［3］祝鑫瑜, 赵海燕, 王莉, 等. 不同负压对不全流产以及子宫内膜损伤的影响［J］. 华中科技大学学报(医学版), 2014, 43(1): 106-108.

［4］Bhartiya D. Pluripotentstem cells in adult tissues: struggling to be acknowledged over two decades［J］. Stem Cell Rev Rep, 2017, 13(6): 713-724.

［5］Argentati C, Morena F, Bazzucchi M,et al. Adiposestem cell translational applications: from benchtobedside［J］. Int J Mol Sci, 2018, 19(11): 3475.

［6］郑友红, 王沂峰. 正常人月经周期子宫内膜变化及机制［J］. 山东医药, 2016, 56(7): 90-91.

［7］段华, 夏恩兰. 宫腔粘连临床诊疗中国专家共识［J］. 中华妇产科杂志, 2015, 50(12): 881-887.

［8］徐洁, 林丹, 李奕. 宫腔粘连的研究进展［J］. 中国计划生育和妇产科, 2017, 9(8): 18-20, 34.

［9］戚亚琴, 王素敏. 宫腔粘连发病机制的研究进展［J］. 医学综述, 2016, 22(5): 932-935.

［10］邓谋, 朱兰. 子宫内膜的再生及宫腔粘连干细胞修复的研究进展［J］. 中国计划生育和妇产科, 2016, 8(3): 6-8，23.

［11］Kasius A, Smit JG, Torrance HL, et al. Endometrial thickness and pregnancy rates after IVF: a systematic review and metaanalysis［J］. Hum Reprod Update, 2014, 20(4): 530-541.

［12］Kumbak B, Erden HF, Tosun S, et al. Outcome of assisted reproduction treatment in patients with endometrial thickness less than 7 mm［J］. Reprod Biomed Online, 2009, 18(1): 79-84.

［13］Gleicher N, Kushnir VA, Barad DH. In reference to ‘Strategies to manage refractory endometrium: state of the art 2016’［J］. Reprod Biomed Online, 2016, 33(5): 604.

［14］Kunicki M, ukaszuk K, WoclawekPotocka I, et al. Evaluation of granulocyte colonystimulating factor effects on treatmentresistant thin endometrium in women undergoing in vitro fertilization［J］. Biomed Res Int, 2014, 2014: 913235.

［15］Zhao J, Zhang Q, Wang Y, et al. Uterine infusion with bone marrow mesenchymal stem cells improves endometrium thickness in a rat model of thin endometrium［J］. Reprod Sci, 2019, 26(12): 1666-1667.

［16］Ding L, Li X, Sun H, et al. Transplantation of bone marrow mesenchymal stem cells on collagen scaffolds for the functional regeneration of injured rat uterus［J］. Biomaterials, 2014, 35(18): 4888-4900.

［17］林彤, 李冬宏, 张鲁榕, 等. 大鼠骨髓间充质干细胞对子宫内膜的损伤修复［J］. 中国妇产科临床杂志, 2019, 20(3): 240-242.

［18］Alawadhi F, Du H, Cakmak H, et al. Bone marrowderived stem cell (BMDSC) transplantation improves fertility in a murine model of asherman′s syndrome［J］. PLoS One, 2014, 9(5): e96662.

［19］Kilic S, Yuksel B, Pinarli F, et al. Effect of stem cell application on asherman syndrome, an experimental rat model［J］. J Assist Reprod Genet, 2014, 31(8): 975-982.

［20］Gugjoo MB, Amarpal, Makhdoomi DM, et al. Equine mesenchymal stem cells: properties, sources, characterization, and potential therapeutic applications［J］. J Equine Vet Sci, 2019, 72: 16-27.

［21］郭意欣, 关婷. 脐带间充质干细胞治疗宫腔粘连的研究现状［J］. 中国妇产科临床杂志, 2017, 18(4): 379-381.

［22］Zhang L, Li Y, Guan CY, et al. Therapeutic effect of human umbilical cordderived mesenchymal stem cells on injured rat endometrium during its chronic phase［J］. Stem Cell Res Ther, 2018, 9(1): 36.

［23］贺桑, 卢永娟, 黄向红，等. 人脐带间充质干细胞移植对大鼠薄型子宫内膜的治疗作用［J］.中国医学前沿杂志(电子版), 2016, 8(9): 67-72.

［24］Xu L, Ding L, Wang L, et al. Umbilical cordderived mesenchymal stem cells on scaffolds facilitate collagen degradation via upregulation of MMP9 in rat uterine scars［J］. Stem Cell Res Ther, 2017, 8(1): 84.

［25］Gan L, Duan H, Xu Q, et al. Human amniotic mesenchymal stromal cell transplantation improves endometrial regeneration in rodent models of intrauterine adhesions［J］. Cytotherapy, 2017, 19(5): 603-616.

［26］Tan J, Li P, Wang Q, et al. Autologous menstrual bloodderived stromal cells transplantation for severe asherman′s syndrome［J］. Hum Reprod, 2016, 31(12): 2723-2729.

［27］Singh N, Mohanty S, Seth T, et al. Autologous stem cell transplantation in refractory Asherman′s syndrome: A novel cell based therapy［J］. Hum Reprod Sci, 2014, 7(2): 93-98.

［28］Nagori CB, Panchal SY, Patel H. Endometrial regeneration using autologous adult stem cells followed by conception by in vitro fertilization in a patient of severe asherman′s syndrome［J］. Hum Reprod Sci, 2011, 4(1): 43-48.

［29］牛婷, 李爱斌, 陈力. 胎盘间充质干细胞修复受损子宫内膜［J］. 中国组织工程研究, 2017, 21(13): 2074-2080.

［30］王香香, 王焱, 杨稍稍, 等. 胎盘间充质干细胞对大鼠子宫内膜损伤的修复作用［J］. 中国医药导报, 2020, 17(10): 18-21.

［31］Witwer KW, Van Balkom B, Bruno S, et al. Defining mesenchymal stromal cell (MSC)derived small extracellular vesicles for therapeutic applications［J］. Extracell Vesicles, 2019, 8(1): 1609206.

［32］Chen CW, Wang LL, Zaman S, et al. Sustained release of endothelial progenitor cellderived extracellular vesicles from shearthinning hydrogels improves angiogenesis and promotes function after myocardial infarction［J］. Cardiovasc Res, 2018, 114(7): 1029-1040.

［33］Ruppert KA, Nguyen TT, Prabhakara KS, et al. Human mesenchymal stromal cellderived extracellular vesicles modify microglial response and improve clinical outcomes in experimental spinal cord injury［J］. Sci Rep, 2018, 8(1): 480.

［34］Seo Y, Kim HS, Hong IS. Stem cellderived extracellular vesicles as immunomodulatory therapeutics［J］. Stem Cells Int, 2019, 2019: 5126156.

［35］Mohammadzadeh A, Pourfathollah AA, Shahrokhi S, et al. Immunomodulatory effects of adiposederived mesenchymal stem cells on the gene expression of major transcription factors of T cell subsets［J］. Int Immunopharmacol, 2014, 20(2): 316-321.

［36］Zhao H, Shang Q, Pan Z, et al. Exosomes from adiposederived stem cells attenuate adipose inflammation and obesity through polarizing M2 macrophages and beiging in white adipose tissue［J］. Diabetes, 2018, 67(2): 235-247.

［37］Ebrahim N, Mostafa O, El Dosoky RE, et al. Human mesenchymal stem cellderived extracellular vesicles/estrogen combined therapy safely ameliorates experimentally induced intrauterine adhesions in a female rat model［J］. Stem Cell Res Ther, 2018, 9(1): 175.

［38］Lopatina T, Bruno S, Tetta C, et al. Plateletderived growth factor regulates the secretion of extracellular vesicles by adipose mesenchymal stem cells and enhances their angiogenic potential［J］. Cell Commun Signal, 2014, 12: 26.

［39］Wang S, Olson EN. AngiomiRs—key regulators of angiogenesis［J］. Curr Opin Genet Dev, 2009, 19(3): 205-211.

［40］赵双丹. 脂肪间充质干细胞来源的外泌体修复宫腔粘连模型大鼠子宫内膜的实验研究［D］. 石家庄：河北医科大学, 2020.

［41］常琦圆. 经血源性间充质干细胞来源外泌体治疗大鼠宫腔粘连的研究［D］. 沈阳：中国医科大学, 2020.

［42］赵双丹, 郑嘉华, 亓文博, 等. 间充质干细胞外泌体应用于生殖系统疾病治疗的作用与机制［J］.中国组织工程研究, 2021, 25(19): 3097-3102.

［43］Han YD, Bai Y, Yan XL, et al. Cotransplantation of exosomes derived from hypoxiapreconditioned adipose mesenchymal stem cells promotes neovascularization and graft survival in fat grafting［J］. Biochem Biophys Res Commun, 2018, 497(1): 305-312.

［44］吕承晓, 段华, 汪沙, 等. 脐带间充质干细胞外泌体转运miR215p促进子宫内膜间质细胞增殖的作用机制［J］. 医学研究生学报, 2020, 33(12): 1262-1268.

［45］胡若萌. 脐带间充质干细胞来源外泌体修复人子宫内膜损伤的初步研究［D］. 合肥：安徽医科大学, 2020.

［46］Yao Y, Chen R, Wang G, et al. Exosomes derived from mesenchymal stem cells reverse EMT via TGFβ1/Smad pathway and promote repair of damaged endometrium［J］. Stem Cell Res Ther, 2019, 10(1): 225.

［47］Xiao B, Zhu Y, Huang J, et al. Exosomal transfer of bone marrow mesenchymal stem cellderived miR340 attenuates endometrial fibrosis［J］. Biol Open, 2019, 8(5): bio039958.

［48］Taylor HS. Endometrial cells derived from donor stem cells in bone marrow transplant recipients［J］. JAMA, 2004, 292(1): 81-85.

［49］Moini A, Zafarani F, Jahangiri N, et al. The effect of vaginal sildenafil on the outcome of assisted reproductive technology cycles in patients with rpeated implantation failures: a randomized placebocontrolled trial［J］. Int J Fertil Steril, 2020, 13(4): 289-295.

［50］Han X, Ma Y, Lu X, et al. Transplantation of human adipose stem cells using a cellular human amniotic membrane improves angiogenesis in injured endometrial tissue in a rat intrauterine adhesion model［J］. Cell Transplant, 2020, 29: 963689720952055.

［51］Yang H, Wu S, Feng R, et al. Vitamin C plus hydrogel facilitates bone marrow stromal cellmediated endometrium regeneration in rats［J］. Stem Cell Res Ther, 2017, 8(1): 267.

［52］Cao Y, Sun H, Zhu H, et al. Allogeneic cell therapy using umbilical cord MSCs on collagen scaffolds for patients with recurrent uterine adhesion: a phase Ⅰ clinical trial［J］. Stem Cell Res Ther, 2018, 9(1): 192.

［53］吴林. 冻干羊膜联合人脐带间充质干细胞治疗中重度宫腔粘连的研究［D］. 衡阳：南华大学, 2020.

［54］Yang L, Liu Y, Wang M, et al. Celastrus orbiculatus extract triggers apoptosis and autophagy via PI3K/Akt/mTOR inhibition in human colorectal cancer cells［J］. Oncol Lett, 2016, 12(5): 3771-3778.

［55］Fruman DA, Rommel C. PI3K and cancer: lessons, challenges and opportunities［J］. Nat Rev Drug Discov, 2014, 13(2): 140-156.

［56］Wang J, Hu R, Xing Q, et al. Exosomes derived from umbilical cord mesenchymal stem cells alleviate mifepristoneinduced human endometrial stromal cell injury［J］. Stem Cells Int, 2020, 2020: 6091269.

［57］张胜辉. 经血源子宫内膜干细胞对子宫内膜损伤的修复作用及机制研究［D］. 新乡：新乡医学院, 2021.

［58］董柳. 人脐带间充质干细胞来源的外泌体对子宫内膜损伤修复的作用及机制研究［D］. 合肥：安徽医科大学, 2021.

［59］Wang L, Hu L, Zhou X, et al. Exosomes secreted by human adipose mesenchymal stem cells promote scarless cutaneous repair by regulating extracellular matrix remodelling［J］. Sci Rep, 2017, 7(1): 13321.

［60］Zhang Y, Lin X, Dai Y, et al. Endometrial stem cells repair injured endometrium and induce angiogenesis via AKT and ERK pathways［J］. Reproduction, 2016, 152(5): 389-402.

［61］Abudukeyoumu A, Li MQ, Xie F. Transforming growth factorβ1 in intrauterine adhesion［J］. Am J Reprod Immunol, 2020, 84(2): e13262.

［62］Li J, Cen B, Chen S, et al. MicroRNA29b inhibits TGFβ1induced fibrosis via regulation of the TGFβ1/Smad pathway in primary human endometrial stromal cells［J］. Mol Med Rep, 2016, 13(5): 4229-4237.

［63］肖向阳,郑德义,王宝云，等.过表达miR34a脂肪干细胞外泌体调控增生性瘢痕成纤维细胞增殖及凋亡的研究［J］.安徽医科大学学报, 2020, 55(6): 887-893.

［64］Herrera J, Henke CA, Bitterman PB. Extracellular matrix as a driver of progressive fibrosis［J］. Clin Invest, 2018, 128(1): 45-53.

［65］Raghunathan VK, Morgan JT, Dreier B, et al. Role of substratum stiffness in modulating genes associated with extracellular matrix and mechanotransducers YAP and TAZ［J］. Invest Ophthalmol Vis Sci, 2013, 54(1): 378-386.

［66］张斯文. 经血来源间充质干细胞联合富血小板血浆治疗大鼠宫腔粘连模型的有效性及作用机制研究［D］. 沈阳：中国医科大学, 2021.

［67］Wang L, Yu C, Chang T, et al. In situ repair abilities of human umbilical cordderived mesenchymal stem cells and autocrosslinked hyaluronic acid gel complex in rhesus monkeys with intrauterine adhesion［J］. Sci Adv, 2020, 6(21): eaba6357.

［68］Shi Q, Sun B, Wang D, et al. Circ6401, a novel circular RNA, is implicated in repair of the damaged endometrium by Wharton′s jellyderived mesenchymal stem cells through regulation of the miR-29b-1-5p/RAP1B axis［J］. Stem Cell Res Ther, 2020, 11(1): 520.