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子宫干细胞:从基础研究到先进的细胞疗法。

Uterine stem cells: from basic research to advanced cell therapies.

机构信息

Reproductive Medicine Department, Igenomix Academy, Paterna (Valencia), Spain.

Reproductive Medicine Department, IVI Barcelona, Barcelona, Spain.

出版信息

Hum Reprod Update. 2018 Nov 1;24(6):673-693. doi: 10.1093/humupd/dmy028.

DOI:10.1093/humupd/dmy028
PMID:30239705
Abstract

BACKGROUND

Stem cell research in the endometrium and myometrium from animal models and humans has led to the identification of endometrial/myometrial stem cells and their niches. This basic knowledge is beginning to be translated to clinical use for incurable uterine pathologies. Additionally, the implication of bone marrow-derived stem cells (BMDSCs) in uterine physiology has opened the field for the exploration of an exogenous and autologous source of stem cells.

OBJECTIVE AND RATIONALE

In this review, we outline the progress of endometrial and myometrial stem/progenitor cells in both human and mouse models from their characterization to their clinical application, indicating roles in Asherman syndrome, atrophic endometrium and tissue engineering, among others.

SEARCH METHODS

A comprehensive search of PubMed and Google Scholar up to December 2017 was conducted to identify peer-reviewed literature related to the contribution of bone marrow, endometrial and myometrial stem cells to potential physiological regeneration as well as their implications in pathologies of the human uterus.

OUTCOMES

The discovery and main characteristics of stem cells in the murine and human endometrium and myometrium are presented together with the relevance of their niches and cross-regulation. The current state of advanced stem cell therapy using BMDSCs in the treatment of Asherman syndrome and atrophic endometrium is analyzed. In the myometrium, the understanding of genetic and epigenetic defects that result in the development of tumor-initiating cells in the myometrial stem niche and thus contribute to the growth of uterine leiomyoma is also presented. Finally, recent advances in tissue engineering based on the creation of novel three-dimensional scaffolds or decellularisation open up new perspectives for the field of uterine transplantation.

WIDER IMPLICATIONS

More than a decade after their discovery, the knowledge of uterine stem cells and their niches is crystalising into novel therapeutic approaches aiming to treat with cells those conditions that cannot be cured with drugs, particularly the currently incurable uterine pathologies. Additional work and improvements are needed, but the basis has been formed for this therapeutic application of uterine cells.

摘要

背景

动物模型和人类的子宫内膜和子宫肌层中的干细胞研究已经导致了子宫内膜/子宫肌层干细胞及其生态位的鉴定。这些基础知识开始被转化为治疗不可治愈的子宫病变的临床应用。此外,骨髓来源的干细胞(BMDSCs)在子宫生理学中的作用也为探索外源性和自体来源的干细胞开辟了新的领域。

目的和理由

在这篇综述中,我们概述了从人类和小鼠模型中鉴定的子宫内膜和子宫肌层干细胞/祖细胞的进展,从它们的特征到它们的临床应用,包括在 Asherman 综合征、萎缩性子宫内膜和组织工程等方面的作用。

搜索方法

对PubMed 和 Google Scholar 进行了全面搜索,截至 2017 年 12 月,以确定与骨髓、子宫内膜和子宫肌层干细胞对潜在生理再生的贡献以及它们在人类子宫病变中的意义相关的同行评议文献。

结果

介绍了鼠类和人类子宫内膜和子宫肌层中干细胞的发现和主要特征,以及它们的生态位和交叉调节的相关性。分析了目前使用 BMDSCs 治疗 Asherman 综合征和萎缩性子宫内膜的高级干细胞治疗的现状。在子宫肌层中,还介绍了遗传和表观遗传缺陷导致子宫肌层干细胞生态位中肿瘤起始细胞的发展,从而促进子宫肌瘤生长的理解。最后,基于创建新型三维支架或脱细胞化的组织工程的最新进展为子宫移植领域开辟了新的前景。

更广泛的影响

在发现它们十多年后,子宫干细胞及其生态位的知识正在结晶成新的治疗方法,旨在用细胞治疗那些不能用药物治愈的疾病,特别是目前无法治愈的子宫病变。还需要更多的工作和改进,但已经为这种子宫细胞的治疗应用奠定了基础。

相似文献

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Uterine stem cells: from basic research to advanced cell therapies.子宫干细胞:从基础研究到先进的细胞疗法。
Hum Reprod Update. 2018 Nov 1;24(6):673-693. doi: 10.1093/humupd/dmy028.
2
Review: Human uterine stem/progenitor cells: Implications for uterine physiology and pathology.综述:人子宫干细胞/祖细胞:对子宫生理学和病理学的影响。
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Tissue-specific stem cells in the myometrium and tumor-initiating cells in leiomyoma.子宫肌层中的组织特异性干细胞和平滑肌瘤中的肿瘤起始细胞。
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Endometrial stem/progenitor cells: the first 10 years.子宫内膜干细胞/祖细胞:首个十年
Hum Reprod Update. 2016 Mar-Apr;22(2):137-63. doi: 10.1093/humupd/dmv051. Epub 2015 Nov 9.
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Therapeutic strategies involving uterine stem cells in reproductive medicine.生殖医学中涉及子宫干细胞的治疗策略。
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