Bi-potential hPSC-derived Müllerian duct-like cells for full-thickness and functional endometrium regeneration.

IF 6.4 1区医学 Q1 CELL & TISSUE ENGINEERING npj Regenerative Medicine Pub Date : 2022-11-23 DOI:10.1038/s41536-022-00263-2

Lin Gong, Nanfang Nie, Xilin Shen, Jingwei Zhang, Yu Li, Yixiao Liu, Jiaqi Xu, Wei Jiang, Yanshan Liu, Hua Liu, Bingbing Wu, XiaoHui Zou

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引用次数: 1

Abstract

Stem cell-based tissue regeneration strategies are promising treatments for severe endometrial injuries. However, there are few appropriate seed cells for regenerating a full-thickness endometrium, which mainly consists of epithelia and stroma. Müllerian ducts in female embryonic development develop into endometrial epithelia and stroma. Hence, we first generated human pluripotent stem cells (hPSC)-derived Müllerian duct-like cells (MDLCs) using a defined and effective protocol. The MDLCs are bi-potent, can gradually differentiate into endometrial epithelial and stromal cells, and reconstitute full-thickness endometrium in vitro and in vivo. Furthermore, MDLCs showed the in situ repair capabilities of reconstructing endometrial structure and recovering pregnancy function in full-thickness endometrial injury rats, and their differentiation fate was revealed by single-cell RNA sequencing (scRNA-seq). Our study provides a strategy for hPSC differentiation into endometrial lineages and an alternative seed cell for injured endometrial regeneration.

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双电位hpsc衍生的勒氏管样细胞用于全层和功能性子宫内膜再生。

基于干细胞的组织再生策略是治疗严重子宫内膜损伤的有希望的方法。然而，很少有合适的种子细胞再生全层子宫内膜，主要由上皮和间质组成。在女性胚胎发育过程中，胚乳管发育为子宫内膜上皮和间质。因此，我们首先使用明确有效的方案生成了人类多能干细胞(hPSC)衍生的勒氏管样细胞(mdlc)。mdlc具有双效性，可逐渐分化为子宫内膜上皮细胞和间质细胞，并在体外和体内重建全层子宫内膜。此外，mdlc在全层子宫内膜损伤大鼠中表现出重建子宫内膜结构和恢复妊娠功能的原位修复能力，并通过单细胞RNA测序(scRNA-seq)揭示了其分化命运。我们的研究为hPSC分化为子宫内膜谱系和损伤子宫内膜再生的替代种子细胞提供了一种策略。

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来源期刊

npj Regenerative Medicine Engineering-Biomedical Engineering

CiteScore

10.00

自引率

1.40%

发文量

审稿时长

12 weeks

期刊介绍： Regenerative Medicine, an innovative online-only journal, aims to advance research in the field of repairing and regenerating damaged tissues and organs within the human body. As a part of the prestigious Nature Partner Journals series and in partnership with ARMI, this high-quality, open access journal serves as a platform for scientists to explore effective therapies that harness the body's natural regenerative capabilities. With a focus on understanding the fundamental mechanisms of tissue damage and regeneration, npj Regenerative Medicine actively encourages studies that bridge the gap between basic research and clinical tissue repair strategies.