经血来源干细胞移植在小鼠卵巢早衰模型中的定位分布

摘要

Objective To evaluate the localization of transplanted human menstrual-derived stem cells (MenSCs)in the premature ovarian failure (POF)mouse model.Methods Mice were intraperitoneally injected with cisplatin to create the POF mouse model.Ninety mice aged 8 weeks were randomly divided into MenSCs transplantation group,POF model group and blank control group.Green fluorescence protein (GFP)-expressing MenSCs were transplanted to MenSCs transplantation group by the tail vein;meanwhile the same volume of PBS was injected into the mice in POF model group and blank control group.Physiological characteristics of mice,serum concentration of FSH and E2,ovarian histology and distribution of green fluorescence signal in the ovarian tissues were assessed in the three groups at 10 days after transplantation.Results Following anorexia and lethargy,the average weight of mice in POF mouse model decreased compared with that in blank control group. The concentration of FSH increased but E2 level decreased significantly in POF model group.Meanwhile,the number of primordial,growing and mature follicles reduced significantly and interstitial fibrosis was observed in the ovary ofPOF model group.After MenSCs transplantation,the average weight of mice in MenSCs transplantation group increased gradually with the improvement of feeding and activities.Ten days after injection of MenSCs,sex hormone levels and the number of follicles returned to normal values.The level of E2 was significantly higher and the level of FSH was lower,while the number of primordial,growing as well as mature follicles in MenSCs transplantation group was significantly higher than that in POF model group.By observing the location of GFP-MenSCs,we found that GFP-positive cells were located in the interstitium but not in follicles,granulose cells,the liver,the kidney,or lung tissue.Conclusion MenSCs can home to the ovary and be located in the interstitium in the POF mouse model.MenSCs can repair ovarian injury and improve endocrine functions of the ovary.%目的 探讨经血来源干细胞(menstrual-derived stem cells,MenSCs)移植在卵巢早衰(premature ovarian failure,POF)小鼠模型中的分布及生长情况.方法 通过腹腔注射顺铂构建POF小鼠模型,90只8周龄雌性C57/BL6小鼠随机分为3组,MenSCs移植组:利用携带绿色荧光蛋白(green fluorescence protein,GFP)基因的慢病毒感染MenSCs进行标记,建模后经尾静脉注射GFP标记的MenSCs悬液(5.0×107个/mL)200μL;POF组:建模后小鼠尾静脉注射等量PBS;空白对照组:正常小鼠不予任何处理仅尾静脉注射等量PBS.观察移植后各组小鼠的一般情况,移植后第10天处死小鼠测定血清FSH和E2浓度、检测卵巢组织学变化、卵泡计数以及检测GFP荧光信号在卵巢内的分布和定位情况.结果 建模后小鼠与空白对照组小鼠比较体质量减轻、食欲减退、活动减少,POF组小鼠FSH水平显著增高,E2水平显著降低,卵巢间质纤维化明显,各级卵泡数均显著减少.MenSCs移植组小鼠自移植后体质量逐渐增加,食欲增强,活动增多,移植后第10天FSH浓度显著低于POF组;E2浓度显著高于POF组;原始卵泡、生长卵泡及成熟卵泡数均显著高于POF组,卵巢间质纤维化程度较POF组减轻,但各项指标仍与空白对照组间存在差异.荧光显微镜下可见GFP-MenSCs定位于卵巢间质,未见于卵泡及颗粒细胞,肝脏、肾脏、肺组织未见GFP绿色荧光信号.结论 MenSCs移植可向POF小鼠卵巢归巢,定位于卵巢间质,对卵巢组织结构及内分泌功能起到修复作用.