Chen Limei, Guo Luopei, Chen Fang, Xie Yu, Zhang Hongwei, Quan Peiqing, Sui Long
Medical Center of Hysteroscopy, Obstetrics and Gynecology Hospital, Fudan University Shanghai, China.
Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Shanghai, China.
Am J Transl Res. 2020 Sep 15;12(9):4941-4954. eCollection 2020.
The ultimate cause of intrauterine adhesions (IUAs) is the substantial destruction of the endometrium, which makes the regeneration of endometrium difficult. The purpose of this study was to observe menstrual blood-derived mesenchymal stem cells (MbMSCs)'s effect on the endometrial regeneration with different methods of transplantation. We also studied whether MbMSCs transfected with the FGF2 gene can improve the regenerative effect.
75 female SD rats with endometrium removed were used as IUA models. These IUA models were divided into 5 groups: group A was the IUA control, group B received a scaffold transplant, group C received a scaffold+MbMSC transplant, group D received a scaffold+FGF2-MbMSC transplant, and group E received FGF2-MbMSCs injected via the tail vein. After the intervention, 5 rats from each group were sacrificed on the 7 day and the 28 day respectively. The distribution of MbMSCs in endometrium was traced using enhanced green fluorescent protein. The endometrial morphology, number of endometrial glands, area of endometrial fibrosis and immunohistochemistry (IHC) of Ki67, VEGF, and CD31 were evaluated. In addition, the fertility of all groups was tested.
On the 7 day after transplantation, enhanced green fluorescent protein showed that there were more MbMSCs in the uterine cavity of group D than that of group E. The endometrial morphology of groups A and B was atrophic and thinned with a high proportion of fibrosis in the endometrium. The endometrium of groups C, D and E was thickened, contained more glands, exhibited reduced fibrosis, and had increased expression of Ki67, VEGF and CD31. The endometrial regenerative effect from high to low was D > C > E with significant differences between each two groups. The fertility test verified the regenerative effect.
These results suggest that the injection of MbMSCs into the tail vein was an effective way to stimulate endometrial regeneration, but the effect was not so well as the intrauterine transplant of MbMSCs with scaffold. The FGF2-transfected MbMSCs exhibited enhanced regenerative effect.
宫腔粘连（IUAs）的根本原因是子宫内膜的大量破坏，这使得子宫内膜再生困难。本研究的目的是观察月经血源性间充质干细胞（MbMSCs）采用不同移植方法对子宫内膜再生的影响。我们还研究了转染FGF2基因的MbMSCs是否能提高再生效果。
将75只切除子宫内膜的雌性SD大鼠作为宫腔粘连模型。这些宫腔粘连模型分为5组：A组为宫腔粘连对照组，B组接受支架移植，C组接受支架+MbMSC移植，D组接受支架+FGF2-MbMSC移植，E组经尾静脉注射FGF2-MbMSCs。干预后，每组分别于第7天和第28天处死5只大鼠。使用增强型绿色荧光蛋白追踪MbMSCs在子宫内膜中的分布。评估子宫内膜形态、子宫内膜腺体数量、子宫内膜纤维化面积以及Ki67、VEGF和CD31的免疫组织化学（IHC）情况。此外，对所有组的生育能力进行检测。
移植后第7天，增强型绿色荧光蛋白显示D组子宫腔内的MbMSCs比E组更多。A组和B组的子宫内膜形态萎缩变薄，子宫内膜纤维化比例高。C组、D组和E组的子宫内膜增厚，腺体增多，纤维化减少，Ki67、VEGF和CD31的表达增加。子宫内膜再生效果从高到低为D>C>E，两两之间差异显著。生育能力检测证实了再生效果。
这些结果表明，经尾静脉注射MbMSCs是刺激子宫内膜再生的有效方法，但效果不如MbMSCs与支架联合宫腔移植。转染FGF2的MbMSCs表现出增强的再生效果。
