Miniature organlike three-dimensional cell clusters often called organoids have emerged as a useful tool for both fundamental and applied bioscience studies. However, there is still a great need to improve the quality of organoids to a level where they exhibit similar biological functionality to an organ. To this end, we hypothesized that a decellularized matrix derived from mesenchymal stem cell (MSC) could regulate the phenotypic and metabolic activity of organoids. This hypothesis was examined by culturing cells of interest in the decellularized matrix of MSCs cultured on a 2D substrate at confluency or in the form of spheroids. The decellularized matrix prepared with MSC spheroids showed a 3D porous structure with a higher content of extracellular matrix molecules than the decellularized matrix derived from MSCs cultured on a 2D substrate. HepG2 hepatocarcinoma cells, which retain the metabolic activity of hepatocytes, were cultured in these decellularized matrices. Interestingly, the decellularized matrix from the MSC spheroids served to develop the hepatic cell clusters with higher levels of E-cadherin-mediated cell–cell adhesion and detoxification activity than the decellularized matrix from the MSCs cultured on a 2D substrate. Overall, the results of this study are useful in improving biological functionality of a wide array of organoids.

中文翻译：

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间充质干细胞产生的脱细胞基质调节肝细胞簇的生长和代谢活性。

微型器官状三维细胞簇（通常称为类器官）已成为基础和应用生物科学研究的有用工具。然而，仍然非常需要将类器官的质量提高到它们具有与器官相似的生物学功能的水平。为此，我们假设从间充质干细胞（MSC）衍生的脱细胞基质可以调节类器官的表型和代谢活性。通过在融合或以类球体形式在2D基质上培养的MSC的脱细胞基质中培养目标细胞来检验该假设。用MSC球体制备的脱细胞基质显示3D多孔结构，其细胞外基质分子含量比在2D基板上培养的MSC脱细胞基质高。在这些脱细胞的基质中培养保留了肝细胞代谢活性的HepG2肝癌细胞。有趣的是，与在2D基质上培养的MSC的脱细胞基质相比，来自MSC球体的脱细胞基质有助于形成具有更高水平的E-钙粘蛋白介导的细胞-细胞粘附和解毒活性的肝细胞簇。总体而言，这项研究的结果可用于改善各种类器官的生物学功能。来自MSC球体的脱细胞基质比具有2D基质培养的MSC的脱细胞基质具有更高的E-钙黏着蛋白介导的细胞间粘附和解毒活性。总体而言，这项研究的结果可用于改善各种类器官的生物学功能。来自MSC球体的脱细胞基质比具有2D基质培养的MSC的脱细胞基质具有更高的E-钙黏着蛋白介导的细胞间粘附和解毒活性。总体而言，这项研究的结果可用于改善各种类器官的生物学功能。