脐带间充质干细胞促进蜕膜血管内皮生长因子表达改善自然流产小鼠妊娠结局  

Umbilical cord mesenchymal stem cells improve pregnancy outcomes of spontaneous abortion mouse models by promoting vascular endothelial growth factor expression in decidua

作　　者：赵鑫鑫 杨晓清[1] 张玉泉[1] Zhao Xinxin;Yang Xiaoqing;Zhang Yuquan(Department of Obstetrics and Gynecology,Affiliated Hospital of Nantong University,Nantong 226001,Jiangsu Province,China)

机构地区：[1]南通大学附属医院妇产科,江苏省南通市226001

出　　处：《中国组织工程研究》2022年第30期4793-4799,共7页Chinese Journal of Tissue Engineering Research

基　　金：江苏省重点研发计划(社会发展)面上项目(BE2018672),项目负责人:张玉泉。

摘　　要：背景:早期自然流产与母胎界面血管形成障碍或异常有关,人脐带华通氏胶间充质干细胞具有向损伤部位迁移及促血管生成的作用,目前人脐带华通氏胶间充质干细胞作用于早期自然流产蜕膜基质细胞的研究尚未有报道。目的:探讨人脐带华通氏胶间充质干细胞对早期自然流产蜕膜基质细胞增殖、凋亡及血管内皮生长因子表达的影响,以及对早期自然流产小鼠妊娠结局的影响。方法:①分离培养早期自然流产和人工流产蜕膜组织,实时荧光定量PCR和Western blot检测蜕膜组织中血管内皮生长因子的表达;②第3代人脐带华通氏胶间充质干细胞和原代自然流产蜕膜基质细胞共培养72 h,EdU、Annexin V-FITC分别检测蜕膜基质细胞增殖和凋亡情况,实时荧光定量PCR和Western blot检测蜕膜基质细胞中血管内皮生长因子的表达;③复制CBA/J×DBA/2自然流产小鼠模型,孕1,3,5 d尾静脉移植人脐带华通氏胶间充质干细胞悬液0.1 mL(细胞浓度为1×1010 L-1),孕14 d计算胚胎吸收率,ELISA检测外周血中血管内皮生长因子水平;实时荧光定量PCR和Western blot检测蜕膜组织中血管内皮生长因子的表达。结果与结论:①与正常蜕膜组织相比,早期自然流产患者蜕膜中血管内皮生长因子表达显著降低;②人脐带华通氏胶间充质干细胞促进早期自然流产蜕膜基质细胞中血管内皮生长因子的表达,促进细胞增殖、抑制细胞凋亡;③人脐带华通氏胶间充质干细胞促进自然流产小鼠蜕膜组织中血管内皮生长因子表达,进而减少胚胎吸收率;④结果表明,合适剂量的人脐带华通氏胶间充质干细胞可以促进蜕膜中血管内皮生长因子表达,改善早期自然流产妊娠结局。BACKGROUND:Early spontaneous abortion is related to the disorder or abnormality of blood vessel formation at the maternal-fetal interface.Human umbilical cord Wharton’s jelly-mesenchymal stem cells can migrate to the injured site and promote angiogenesis.However,the effect of human Wharton’s jellymesenchymal stem cells on decidual stromal cells has not been studied yet.OBJECTIVE:To investigate the effect of human Wharton’s jelly-mesenchymal stem cells on proliferation and apoptosis of decidual stromal cells from early spontaneous abortion women and vascular endothelial growth factor expression,and to explore its effect on the pregnancy outcome of early spontaneous abortion mice.METHODS:(1)Early spontaneous abortion and artificial abortion decidual tissues were separated and cultured.Real-time fluorescent quantitative PCR and western blot assay were utilized to detect the expression of vascular endothelial growth factor in decidua tissue.(2)The third passage of human umbilical cord Wharton’s jelly-mesenchymal stem cells and primary spontaneous abortion decidual stromal cells were co-cultured for 72 hours.EdU and Annexin V-FITC were applied to detect the proliferation and apoptosis of decidual stromal cells,respectively.Real-time fluorescent quantitative PCR and western blot assay were used to detect the expression of vascular endothelial growth factor in decidual stromal cells.(3)After reproducing the CBA/J×DBA/2 spontaneous abortion mouse model,human umbilical cord Wharton’s jelly-mesenchymal stem cell suspension 0.1 mL(cell concentration:1×10^(10) L^(-1))was transplanted into the tail vein at 1,3,and 5 days after pregnancy.The embryo absorption rate was calculated at 14 days of pregnancy.ELISA was used to detect the level of vascular endothelial growth factor in peripheral blood.Real-time fluorescent quantitative PCR and western blot assay were employed to detect the expression of vascular endothelial growth factor in decidua tissue.RESULTS AND CONCLUSION:(1)Compared with normal decidua tissue,expres

关 键 词：自然流产 血管内皮生长因子 蜕膜基质细胞 人脐带华通氏胶间充质干细胞 小鼠流产模型 

分 类 号：R453.9[医药卫生—治疗学] R394.2[医药卫生—临床医学]