Stem cell-like properties of the endometrial side population: implication in endometrial regeneration.
Stem cell-like properties of the endometrial side population: implication in endometrial regeneration.
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DOI：
10.1371/journal.pone.0010387
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发表时间：
2010-04-28
期刊：
影响因子：
3.7
通讯作者：
Okano H
中科院分区：
文献类型：
--
作者：
Masuda H;Matsuzaki Y;Hiratsu E;Ono M;Nagashima T;Kajitani T;Arase T;Oda H;Uchida H;Asada H;Ito M;Yoshimura Y;Maruyama T;Okano H
人类子宫内膜在女性的整个生殖生活中经历周期性再生。子宫内膜细胞通过逆行月经异位植入引起子宫内膜病变，影响约10%的育龄妇女。人子宫内膜在在位和异位部位的高再生能力表明存在干/祖细胞和独特的血管生成系统。本研究的目的是分离和鉴定推定的子宫内膜干/祖细胞，并说明它们如何参与子宫内膜的生理学。我们发现，从人子宫内膜获得的总细胞中约有2%显示侧群（SP）表型，通过Hoechst染色细胞的流式细胞术分析确定。子宫内膜SP（ESP）细胞表现出优先表达的几个内皮细胞标志物相比，子宫内膜主群体（EMP）细胞。内皮细胞特异性培养液能使ESP细胞在体外增殖并分化为不同类型的子宫内膜细胞，包括腺上皮细胞、间质细胞和内皮细胞，而在同一培养液中，EMP细胞仅分化为间质细胞。此外，ESP细胞，而不是EMP细胞，重建组织子宫内膜组织与轮廓分明的腺体结构时，移植到肾包膜下的严重免疫缺陷小鼠。值得注意的是，ESP细胞产生的内皮细胞迁移到小鼠肾实质中并形成成熟的血管。这种在体内血管生成和子宫内膜细胞再生的潜力在ESP组分中比在EMP组分中更突出，因为后者主要在体内产生基质细胞。这些结果表明，推定的子宫内膜干细胞高度富集在ESP细胞中。这些独特的特征表明，ESP细胞可能驱动生理性子宫内膜再生，并参与子宫内膜异位症的发病机制。
The human endometrium undergoes cyclical regeneration throughout a woman's reproductive life. Ectopic implantation of endometrial cells through retrograde menstruation gives rise to endometriotic lesions which affect approximately 10% of reproductive-aged women. The high regenerative capacity of the human endometrium at eutopic and ectopic sites suggests the existence of stem/progenitor cells and a unique angiogenic system. The objective of this study was to isolate and characterize putative endometrial stem/progenitor cells and to address how they might be involved in the physiology of endometrium. We found that approximately 2% of the total cells obtained from human endometrium displayed a side population (SP) phenotype, as determined by flow cytometric analysis of Hoechst-stained cells. The endometrial SP (ESP) cells exhibited preferential expression of several endothelial cell markers compared to endometrial main population (EMP) cells. A medium specific for endothelial cell culture enabled ESP cells to proliferate and differentiate into various types of endometrial cells, including glandular epithelial, stromal and endothelial cells in vitro, whereas in the same medium, EMP cells differentiated only into stromal cells. Furthermore, ESP cells, but not EMP cells, reconstituted organized endometrial tissue with well-delineated glandular structures when transplanted under the kidney capsule of severely immunodeficient mice. Notably, ESP cells generated endothelial cells that migrated into the mouse kidney parenchyma and formed mature blood vessels. This potential for in vivo angiogenesis and endometrial cell regeneration was more prominent in the ESP fraction than in the EMP fraction, as the latter mainly gave rise to stromal cells in vivo. These results indicate that putative endometrial stem cells are highly enriched in the ESP cells. These unique characteristics suggest that ESP cells might drive physiological endometrial regeneration and be involved in the pathogenesis of endometriosis.