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工程化干细胞衍生细胞外基质:脱细胞化、表征和生物学功能。

Engineering Stem Cell-Derived Extracellular Matrices: Decellularization, Characterization, and Biological Function.

机构信息

Hydrodynamics Laboratory, CNRS UMR7646, Ecole Polytechnique, Palaiseau, France.

Laboratory of Physical Microfluidics and Bioengineering, Department of Genome and Genetics, Institut Pasteur, Paris, France.

出版信息

Tissue Eng Part B Rev. 2020 Oct;26(5):402-422. doi: 10.1089/ten.TEB.2019.0349. Epub 2020 Apr 28.

DOI:10.1089/ten.TEB.2019.0349
PMID:32220216
Abstract

Stem cells, including mesenchymal stem cells and pluripotent stem cells, have attracted considerable attention in tissue engineering and regenerative medicine primarily because of their unique ability in self-renewal and multilineage differentiation. However, stem cells also have important secretory functions that form a specialized microenvironment and direct tissue development and regeneration. Extracellular matrices (ECMs) derived from stem cells retain the functional properties of their native environment and exhibit unique signaling that mediates stem cell self-renewal and lineage commitment. Stem cell-derived ECMs (scECMs) also have tunable properties corresponding to their developmental stages, suggesting that their lineage- and developmental specificity can be engineered for a wide range of applications. Hence, there is a growing interest in reconstructing stem cell microenvironment through decellularization and obtaining decellularized matrices that exhibit unique biological properties. This article summarizes recent advances in the use and understanding of scECMs. Moreover, future directions to extend the spectrum of applications of stem-derived ECMs in tissue engineering by comprehensively elucidating and engineering their regulatory function is highlighted. Impact statement Stem cells bear unique potency for multilineage differentiation as well as the capacity to secrete a vast amount of regulatory molecules. At different developmental stages, the extracellular matrices (ECMs) secreted by stem cells regulate their microenvironment and direct tissue development. The decellularization of stem cells effectively preserves ECM functional properties and can provide suitable templates to regulate stem cell fate decision, which can hardly be reproduced using single ECM proteins or synthetic scaffolds. This review highlights the unique regulatory functions of stem cell-derived ECMs, which can serve as novel sources of highly bioactive materials for tissue engineering and cell therapy.

摘要

干细胞,包括间充质干细胞和多能干细胞,因其独特的自我更新和多能分化能力,在组织工程和再生医学中受到了广泛关注。然而,干细胞还具有重要的分泌功能,能形成特化的微环境,并指导组织发育和再生。源自干细胞的细胞外基质 (ECM) 保留了其固有环境的功能特性,并表现出独特的信号转导,调节干细胞的自我更新和谱系分化。干细胞衍生的细胞外基质 (scECM) 还具有与其发育阶段相对应的可调特性,表明其谱系和发育特异性可以针对广泛的应用进行工程设计。因此,通过脱细胞化来重建干细胞微环境并获得表现出独特生物学特性的脱细胞基质的方法越来越受到关注。本文总结了 scECM 的应用和理解方面的最新进展。此外,还强调了通过全面阐明和工程设计其调控功能来扩展干细胞衍生 ECM 在组织工程中的应用范围的未来方向。 影响评估 干细胞具有多能分化的独特潜力,以及分泌大量调节分子的能力。在不同的发育阶段,干细胞分泌的细胞外基质 (ECM) 调节其微环境并指导组织发育。干细胞的脱细胞化有效地保留了 ECM 的功能特性,并能提供合适的模板来调节干细胞命运决定,这是使用单个 ECM 蛋白或合成支架很难复制的。本文强调了干细胞衍生 ECM 的独特调控功能,它们可作为组织工程和细胞治疗的新型高生物活性材料来源。

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