Three-dimensional migration of human amniotic fluid stem cells involves mesenchymal and amoeboid modes and is regulated by mTORC1,STEM CELLS

当前位置： X-MOL 学术 › STEM CELLS › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Three-dimensional migration of human amniotic fluid stem cells involves mesenchymal and amoeboid modes and is regulated by mTORC1
STEM CELLS ( IF 4.0 ) Pub Date : 2021-07-31 , DOI: 10.1002/stem.3441
Margit Rosner ₁ , Markus Hengstschläger ₁

Affiliation

Three-dimensional (3D) cell migration is an integral part of many physiologic processes. Although being well studied in the context of adult tissue homeostasis and cancer development, remarkably little is known about the invasive behavior of human stem cells. Using two different kinds of invasion assays, this study aimed at investigating and characterizing the 3D migratory capacity of human amniotic fluid stem cells (hAFSCs), a well-established fetal stem cell type. Eight hAFSC lines were found to harbor pronounced potential to penetrate basement membrane (BM)-like matrices. Morphological examination and inhibitor approaches revealed that 3D migration of hAFSCs involves both the matrix metalloprotease-dependent mesenchymal, elongated mode and the Rho-associated protein kinase-dependent amoeboid, round mode. Moreover, hAFSCs could be shown to harbor transendothelial migration capacity and to exhibit a motility-associated marker expression pattern. Finally, the potential to cross extracellular matrix was found to be induced by mTORC1-activating growth factors and reduced by blocking mTORC1 activity. Taken together, this report provides the first demonstration that human stem cells exhibit mTORC1-dependent invasive capacity and can concurrently make use of mesenchymal and amoeboid 3D cell migration modes, which represents an important step toward the full biological characterization of fetal human stem cells with relevance to both developmental research and stem cell-based therapy.

中文翻译：

人羊水干细胞的三维迁移涉及间充质和变形虫模式，受mTORC1调控

三维 (3D) 细胞迁移是许多生理过程的组成部分。尽管在成人组织稳态和癌症发展的背景下进行了很好的研究，但对人类干细胞的侵袭行为知之甚少。本研究使用两种不同的入侵检测方法，旨在调查和表征人羊水干细胞 (hAFSCs) 的 3D 迁移能力，这是一种成熟的胎儿干细胞类型。8 个 hAFSC 系被发现具有明显的穿透基底膜 (BM) 样基质的潜力。形态学检查和抑制剂方法表明，hAFSCs 的 3D 迁移涉及基质金属蛋白酶依赖性间充质细长模式和 Rho 相关蛋白激酶依赖性变形虫圆形模式。而且，hAFSCs 可以显示出具有跨内皮迁移能力并表现出与运动相关的标记表达模式。最后，发现通过 mTORC1 激活生长因子诱导并通过阻断 mTORC1 活性降低了穿过细胞外基质的潜力。总之，本报告首次证明人类干细胞表现出 mTORC1 依赖的侵袭能力，并且可以同时利用间充质和变形虫 3D 细胞迁移模式，这代表了朝着具有相关性的胎儿人类干细胞的完整生物学特征迈出的重要一步发展研究和基于干细胞的治疗。发现穿过细胞外基质的潜力是由激活 mTORC1 的生长因子诱导的，并通过阻断 mTORC1 活性而降低。总之，本报告首次证明人类干细胞表现出 mTORC1 依赖的侵袭能力，并且可以同时利用间充质和变形虫 3D 细胞迁移模式，这代表了朝着具有相关性的胎儿人类干细胞的完整生物学特征迈出的重要一步发展研究和基于干细胞的治疗。发现穿过细胞外基质的潜力是由激活 mTORC1 的生长因子诱导的，并通过阻断 mTORC1 活性而降低。总之，本报告首次证明人类干细胞表现出 mTORC1 依赖的侵袭能力，并且可以同时利用间充质和变形虫 3D 细胞迁移模式，这代表了朝着具有相关性的胎儿人类干细胞的完整生物学特征迈出的重要一步发展研究和基于干细胞的治疗。

更新日期：2021-07-31

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11