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Bone Marrow Stem Cells do Not Contribute to Endometrial Cell Lineages in Chimeric Mouse Models
STEM CELLS ( IF 4.0 ) Pub Date : 2017-10-04 , DOI: 10.1002/stem.2706 Yih Rue Ong 1 , Fiona L. Cousins 1, 2 , Xiaoqing Yang 1, 3 , Ahmed Aedh A. Al Mushafi 1 , David T. Breault 4 , Caroline E. Gargett 1, 2 , James A. Deane 1, 2
STEM CELLS ( IF 4.0 ) Pub Date : 2017-10-04 , DOI: 10.1002/stem.2706 Yih Rue Ong 1 , Fiona L. Cousins 1, 2 , Xiaoqing Yang 1, 3 , Ahmed Aedh A. Al Mushafi 1 , David T. Breault 4 , Caroline E. Gargett 1, 2 , James A. Deane 1, 2
Affiliation
Studies from five independent laboratories conclude that bone marrow stem cells transdifferentiate into endometrial stroma, epithelium, and endothelium. We investigated the nature of bone marrow‐derived cells in the mouse endometrium by reconstituting irradiated wild type recipients with bone marrow containing transgenic mTert‐green fluorescent protein (GFP) or chicken β‐actin (Ch β‐actin)‐GFP reporters. mTert‐GFP is a telomerase marker identifying hematopoietic stem cells and subpopulations of epithelial, endothelial, and immune cells in the endometrium. Ch β‐actin‐GFP is a ubiquitous reporter previously used to identify bone marrow‐derived cells in the endometrium. Confocal fluorescence microscopy for GFP and markers of endometrial and immune cells were used to characterize bone marrow‐derived cells in the endometrium of transplant recipients. No evidence of GFP+ bone marrow‐derived stroma, epithelium, or endothelium was observed in the endometrium of mTert‐GFP or Ch β‐actin‐GFP recipients. All GFP+ cells detected in the endometrium were immune cells expressing the pan leukocyte marker CD45, including CD3+ T cells and F4/80+ macrophages. Further examination of the Ch β‐actin‐GFP transplant model revealed that bone marrow‐derived F4/80+ macrophages immunostained weakly for CD45. These macrophages were abundant in the stroma, infiltrated the epithelial and vascular compartments, and could easily be mistaken for bone marrow‐derived endometrial cells. We conclude that it is unlikely that bone marrow cells are able to transdifferentiate into endometrial stroma, epithelium, and endothelium. This result has important therapeutic implications, as the expectation that bone marrow stem cells contribute directly to endometrial regeneration is shaping strategies designed to regenerate endometrium in Asherman's syndrome and to control aberrant endometrial growth in endometriosis. Stem Cells 2018;36:91–102
中文翻译:
骨髓干细胞对嵌合小鼠模型中的子宫内膜细胞谱系没有贡献
来自五个独立实验室的研究得出结论,骨髓干细胞可转分化为子宫内膜基质、上皮和内皮。我们通过用含有转基因 mTert-绿色荧光蛋白 (GFP) 或鸡 β-肌动蛋白 (Ch β-肌动蛋白)-GFP 报告基因的骨髓重建受照射的野生型受体,研究了小鼠子宫内膜中骨髓衍生细胞的性质。mTert-GFP 是一种端粒酶标记物,可识别子宫内膜中的造血干细胞和上皮细胞、内皮细胞和免疫细胞亚群。Ch β-actin-GFP 是一种普遍存在的报告基因,以前用于鉴定子宫内膜中的骨髓衍生细胞。GFP 的共聚焦荧光显微镜以及子宫内膜和免疫细胞的标记用于表征移植受者子宫内膜中的骨髓衍生细胞。在 mTert-GFP 或 Ch β-肌动蛋白-GFP 受体的子宫内膜中没有观察到 GFP+ 骨髓来源的基质、上皮或内皮的证据。在子宫内膜中检测到的所有 GFP+ 细胞都是表达泛白细胞标志物 CD45 的免疫细胞,包括 CD3+ T 细胞和 F4/80+ 巨噬细胞。对 Ch β-actin-GFP 移植模型的进一步检查显示,骨髓来源的 F4/80+ 巨噬细胞对 CD45 的免疫染色较弱。这些巨噬细胞在基质中丰富,浸润上皮和血管隔室,很容易被误认为是骨髓来源的子宫内膜细胞。我们得出结论,骨髓细胞不太可能转分化为子宫内膜基质、上皮和内皮。这一结果具有重要的治疗意义,由于对骨髓干细胞直接促进子宫内膜再生的期望正在塑造旨在再生阿舍曼综合征子宫内膜和控制子宫内膜异位症中异常子宫内膜生长的策略。干细胞 2018;36:91–102
更新日期:2017-10-04
中文翻译:
骨髓干细胞对嵌合小鼠模型中的子宫内膜细胞谱系没有贡献
来自五个独立实验室的研究得出结论,骨髓干细胞可转分化为子宫内膜基质、上皮和内皮。我们通过用含有转基因 mTert-绿色荧光蛋白 (GFP) 或鸡 β-肌动蛋白 (Ch β-肌动蛋白)-GFP 报告基因的骨髓重建受照射的野生型受体,研究了小鼠子宫内膜中骨髓衍生细胞的性质。mTert-GFP 是一种端粒酶标记物,可识别子宫内膜中的造血干细胞和上皮细胞、内皮细胞和免疫细胞亚群。Ch β-actin-GFP 是一种普遍存在的报告基因,以前用于鉴定子宫内膜中的骨髓衍生细胞。GFP 的共聚焦荧光显微镜以及子宫内膜和免疫细胞的标记用于表征移植受者子宫内膜中的骨髓衍生细胞。在 mTert-GFP 或 Ch β-肌动蛋白-GFP 受体的子宫内膜中没有观察到 GFP+ 骨髓来源的基质、上皮或内皮的证据。在子宫内膜中检测到的所有 GFP+ 细胞都是表达泛白细胞标志物 CD45 的免疫细胞,包括 CD3+ T 细胞和 F4/80+ 巨噬细胞。对 Ch β-actin-GFP 移植模型的进一步检查显示,骨髓来源的 F4/80+ 巨噬细胞对 CD45 的免疫染色较弱。这些巨噬细胞在基质中丰富,浸润上皮和血管隔室,很容易被误认为是骨髓来源的子宫内膜细胞。我们得出结论,骨髓细胞不太可能转分化为子宫内膜基质、上皮和内皮。这一结果具有重要的治疗意义,由于对骨髓干细胞直接促进子宫内膜再生的期望正在塑造旨在再生阿舍曼综合征子宫内膜和控制子宫内膜异位症中异常子宫内膜生长的策略。干细胞 2018;36:91–102