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基质解码——一种具有引导人诱导多能干细胞分化的器官特异性信号的胰腺细胞外基质。

Matrix decoded - A pancreatic extracellular matrix with organ specific cues guiding human iPSC differentiation.

作者信息

Berger Constantin, Bjørlykke Yngvild, Hahn Lukas, Mühlemann Markus, Kress Sebastian, Walles Heike, Luxenhofer Robert, Ræder Helge, Metzger Marco, Zdzieblo Daniela

机构信息

Chair Tissue Engineering and Regenerative Medicine, University Hospital Würzburg, Würzburg, Germany.

Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Pediatrics, Haukeland University Hospital, Bergen, Norway.

出版信息

Biomaterials. 2020 Jun;244:119766. doi: 10.1016/j.biomaterials.2020.119766. Epub 2020 Mar 6.

DOI:10.1016/j.biomaterials.2020.119766
PMID:32199284
Abstract

The extracellular matrix represents a dynamic microenvironment regulating essential cell functions in vivo. Tissue engineering approaches aim to recreate the native niche in vitro using biological scaffolds generated by organ decellularization. So far, the organ specific origin of such scaffolds was less considered and potential consequences for in vitro cell culture remain largely elusive. Here, we show that organ specific cues of biological scaffolds affect cellular behavior. In detail, we report on the generation of a well-preserved pancreatic bioscaffold and introduce a scoring system allowing standardized inter-study quality assessment. Using multiple analysis tools for in-depth-characterization of the biological scaffold, we reveal unique compositional, physico-structural, and biophysical properties. Finally, we prove the functional relevance of the biological origin by demonstrating a regulatory effect of the matrix on multi-lineage differentiation of human induced pluripotent stem cells emphasizing the significance of matrix specificity for cellular behavior in artificial microenvironments.

摘要

细胞外基质代表一种动态微环境,在体内调节细胞的基本功能。组织工程方法旨在利用通过器官去细胞化产生的生物支架在体外重建天然生态位。到目前为止,此类支架的器官特异性来源较少被考虑,其对体外细胞培养的潜在影响在很大程度上仍不清楚。在此,我们表明生物支架的器官特异性线索会影响细胞行为。具体而言,我们报告了一种保存良好的胰腺生物支架的生成,并引入了一种评分系统,用于标准化研究间的质量评估。使用多种分析工具对生物支架进行深入表征,我们揭示了其独特的组成、物理结构和生物物理特性。最后,我们通过证明该基质对人类诱导多能干细胞多谱系分化的调节作用,证实了生物来源的功能相关性,强调了基质特异性对人工微环境中细胞行为的重要性。

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