Contribution of different bone marrow-derived cell types in endometrial regeneration using an irradiated murine model
Contribution of different bone marrow-derived cell types in endometrial regeneration using an irradiated murine model
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DOI：
10.1016/j.fertnstert.2015.02.030
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发表时间：
2015-06-01
影响因子：
6.7
通讯作者：
Simon, Carlos
中科院分区：
文献类型：
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作者：
Gil-Sanchis, Claudia;Cervello, Irene;Simon, Carlos
目的：探讨7种骨髓来源细胞在小鼠全身照射后子宫内膜再生中的作用。设计：前瞻性实验动物研究。地点：大学实验室。动物(S)：转β-肌动蛋白绿色荧光蛋白基因C57BL/6-TG(CAG-EGFP)和C57BL/6J雌性小鼠。干预(S)：取自CAG-EGFP小鼠的骨髓细胞：未分离的骨髓细胞、造血祖细胞、内皮祖细胞和间充质干细胞。此外，还使用了三种小鼠GFP(+)细胞系：小鼠Oct4阴性的BMDC多能成体祖细胞(mOct4(-)BM-MAPC)、BMDC低母细胞样干细胞(mOct4(+)BM-HypoSCs)和MSCs。主要观察指标(S)：流式细胞术、细胞培养、骨髓移植试验、组织学评价、免疫组织化学、细胞增殖、细胞凋亡及统计学分析。结果(S)：12周后，组织学分析显示mOct4(-)BM-MAPC和MSC系小鼠子宫明显小于未培养BMDCs组和mOct4(+)BM-HypoSCs组。移植GFP(+)细胞的百分率为0.13%~4.78%。BMDCs处理组小鼠子宫中Ki-67的表达低于对照组，而内皮祖细胞组和mOct4(+)BM-HypoSCs组的TUNEL+细胞数明显高于对照组。结论：在再生子宫内膜中可见少量的BMDCs，包括间质、内皮和上皮室。新鲜分离的MSCs和EPC联合mOct4(+)BM-HypoSCs诱导的再生程度最大，而培养分离的MSCs和mOct4(-)BM-MAPC移植可能对子宫内膜再生有抑制作用。(C)2015年，由美国生殖医学学会提供。
Objective: To study the involvement of seven types of bone marrow-derived cells (BMDCs) in the endometrial regeneration in mice after total body irradiation.Design: Prospective experimental animal study.Setting: University research laboratories.Animal(s): beta-Actin-green fluorescent protein (GFP) transgenic C57BL/6-Tg (CAG-EGFP) and C57BL/6J female mice.Intervention(s): The BMDCs were isolated from CAG-EGFP mice: unfractionated bone marrow cells, hematopoietic progenitor cells, endothelial progenitor cells (EPCs), and mesenchymal stem cells (MSCs). In addition three murine GFP(+) cell lines were used: mouse Oct4 negative BMDC multipotent adult progenitor cells (mOct4(-)BM-MAPCs), BMDC hypoblast-like stem cells (mOct4(+) BM-HypoSCs), and MSCs. All cell types were injected through the tail vein of 9 Gy-irradiated C57BL/6J female mice.Main Outcome Measure(s): Flow cytometry, cell culture, bone marrow transplantation assays, histologic evaluation, immunohistochemistry, proliferation, apoptosis, and statistical analysis.Result(s): After 12 weeks, histologic analysis revealed that uteri of mice with mOct4(-)BM-MAPCs and MSC line were significantly smaller than uteri of mice with uncultured BMDCs or mOct4(+) BM-HypoSCs. The percentage of engrafted GFP(+) cells ranged from 0.13%-4.78%. Expression of Ki-67 was lower in all uteri from BMDCs treated mice than in the control, whereas TUNEL+ cells were increased in the EPCs and mOct4(+)BM-HypoSCs groups.Conclusion(s): Low number of some BMDCs can be found in regenerating endometrium, including stromal, endotelial, and epithelial compartments. Freshly isolated MSCs and EPCs together with mOct4(+) BM-HypoSCs induced the greatest degree of regeneration, whereas culture isolated MSCs and mOct4(-)BM-MAPCs transplantation may have an inhibitory effect on endometrial regeneration. (C) 2015 by American Society for Reproductive Medicine.