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人子宫中的干细胞/祖细胞及其再生潜能

Stem/progenitor cells and the regeneration potentials in the human uterus.

作者信息

Maruyama Tetsuo

机构信息

Department of Obstetrics and Gynecology Keio University School of Medicine 35, Shinanomachi, Shinjuku-ku 160-8582 Tokyo Japan.

出版信息

Reprod Med Biol. 2009 Aug 26;9(1):9-16. doi: 10.1007/s12522-009-0032-y. eCollection 2010 Mar.

Abstract

The human uterus is unique in that it possesses the tremendous regenerative capacity required for cyclical regeneration and remodeling throughout a woman's reproductive life. Not only must the uterus rapidly enlarge to accommodate the developing fetus, the endometrium must also regenerate with each menstrual cycle. This plasticity of the reproductive system has recently been highlighted. My research group and collaborators showed that functional endometrial tissue could be regenerated from only a small number of singly dispersed human endometrial cells, transplanted beneath the kidney capsule of severely immunodeficient mice. This artificially generated endometrium resembles the natural endometrium, and contains human blood vessels that invade the mouse kidney parenchyma. Additionally, it mimics normal hormone-dependent changes including proliferation, differentiation, and tissue breakdown (menstruation). The regenerative capacity of endometrial cells makes them ideal candidates for tissue reconstitution, angiogenesis, and human-mouse chimeric vessel formation. The smooth muscle cells of the uterus (myometrium) share the plasticity of the endometrium. This is evidenced by their capacity for dramatic, repeatable, pregnancy-induced enlargement. Regeneration and remodeling in the female reproductive tract allude to the existence of endometrial and myometrial stem cell systems. We have recently isolated candidate populations of adult stem cells from both the human endometrium and myometrium. Characterization of these endometrial and myometrial cells, along with the study of the mechanisms controlling their regeneration, will improve the understanding of the physiology and pathophysiology of the female reproductive tract. Furthermore, myometrial and endometrial stem-like cells might also represent a novel source of biological material that could be used for the reconstruction of not only the human uterus but other organs as well.

摘要

人类子宫具有独特之处,即它具备在女性整个生殖生命周期中进行周期性再生和重塑所需的巨大再生能力。子宫不仅要迅速增大以容纳发育中的胎儿,子宫内膜还必须在每个月经周期进行再生。生殖系统的这种可塑性最近受到了关注。我所在的研究小组及合作者发现,仅从少量单个分散的人类子宫内膜细胞就能再生出功能性子宫内膜组织,并将其移植到严重免疫缺陷小鼠的肾包膜下。这种人工生成的子宫内膜类似于天然子宫内膜,且含有侵入小鼠肾实质的人类血管。此外,它还能模拟正常的激素依赖性变化,包括增殖、分化和组织分解(月经)。子宫内膜细胞的再生能力使其成为组织重建、血管生成和人鼠嵌合血管形成的理想候选者。子宫的平滑肌细胞(子宫肌层)也具有与子宫内膜相同的可塑性。这一点可通过它们在妊娠时能够显著、反复增大得到证明。女性生殖道的再生和重塑暗示着子宫内膜和子宫肌层干细胞系统的存在。我们最近已从人类子宫内膜和子宫肌层中分离出了成体干细胞的候选群体。对这些子宫内膜和子宫肌层细胞的特性进行表征,以及对控制其再生机制的研究,将有助于增进对女性生殖道生理和病理生理的理解。此外,子宫肌层和子宫内膜的类干细胞也可能代表一种新型生物材料来源,不仅可用于人类子宫的重建,还可用于其他器官的重建。

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本文引用的文献

2
Endometriosis.子宫内膜异位症
N Engl J Med. 2009 Jan 15;360(3):268-79. doi: 10.1056/NEJMra0804690.
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Pluripotent stem cell lines.多能干细胞系
Genes Dev. 2008 Aug 1;22(15):1987-97. doi: 10.1101/gad.1689808.
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In vivo imaging in humanized mice.人源化小鼠体内成像。
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