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去细胞化组织/器官细胞外基质生物墨水定向诱导多能成体干细胞的差异化行为。

Directed differential behaviors of multipotent adult stem cells from decellularized tissue/organ extracellular matrix bioinks.

机构信息

Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, 37673, Republic of Korea.

Department of Mechanical Engineering, Pohang University of Science and Technology, Pohang, 37673, Republic of Korea.

出版信息

Biomaterials. 2019 Dec;224:119496. doi: 10.1016/j.biomaterials.2019.119496. Epub 2019 Sep 12.

Abstract

The decellularized tissue/organ extracellular matrix (dECM) is a naturally derived biomaterial that inherits various functional components from the native tissue or organ. Recently, various kinds of tissue/organ dECM bioinks capable of encapsulating cells, combined with 3D cell printing, have enabled remarkable progress in tissue engineering and regenerative medicine. However, the way in which the dECM component compositions of each tissue of different origins interact with cells and dictate tissue-specific cell behavior in the 3D microenvironment remains mostly unknown. To address this issue, in-depth differential proteomic analyses of four porcine dECMs were performed. Specifically, the differential variations of matrisome protein composition in each decellularized tissue type were also uncovered, which can play a significant role by affecting the resident cells in specific tissues. Furthermore, microarray analyses of human bone marrow mesenchymal stem cells (hBMMSCs) printed with various dECM bioinks were conducted to reveal the effect of compositional variations in a tissue-specific manner at the cellular level depending on the multipotency of MSCs. Through whole transcriptome analysis, differential expression patterns of genes were observed in a tissue-specific manner, and this research provides strong evidence of the tissue-specific functionalities of dECM bioinks.

摘要

去细胞化组织/器官细胞外基质 (dECM) 是一种天然衍生的生物材料,它从天然组织或器官中继承了各种功能成分。最近,各种能够包埋细胞的组织/器官 dECM 生物墨水与 3D 细胞打印相结合,在组织工程和再生医学方面取得了显著进展。然而,不同来源的每种组织的 dECM 成分组合与细胞相互作用并决定 3D 微环境中组织特异性细胞行为的方式在很大程度上仍然未知。为了解决这个问题,对四种猪 dECM 进行了深入的差异蛋白质组学分析。具体来说,还揭示了每种去细胞化组织类型中基质蛋白组成的差异变化,这些变化可以通过影响特定组织中的常驻细胞来发挥重要作用。此外,还对用各种 dECM 生物墨水打印的人骨髓间充质干细胞 (hBMMSCs) 进行了微阵列分析,以揭示细胞水平上特定于组织的组成变化对 MSC 多能性的影响。通过全转录组分析,观察到基因以组织特异性的方式表现出差异表达模式,这项研究为 dECM 生物墨水的组织特异性功能提供了有力证据。

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