The differentiation of MSCs into functional hepatocyte-like cells in a liver biomatrix scaffold and their transplantation into liver-fibrotic mice
The differentiation of MSCs into functional hepatocyte-like cells in a liver biomatrix scaffold and their transplantation into liver-fibrotic mice
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MSC 在肝脏生物基质支架中分化为功能性肝细胞样细胞并将其移植到肝纤维化小鼠中
DOI：
10.1016/j.biomaterials.2012.08.058
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发表时间：
2012-12-01
期刊：
影响因子：
14
通讯作者：
Dou, Kefeng
中科院分区：
文献类型：
--
作者：
Ji, Ru;Zhang, Ning;Dou, Kefeng
间充质干细胞（MSCs）衍生的肝细胞在肝脏疾病的细胞治疗中具有巨大的潜力。基于细胞的治疗严重依赖于MSCs的肝分化，并具有高效率和相当规模。最近的研究结果表明，脱细胞器官为干细胞成熟的谱系限制提供了三维细胞外基质。在这项研究中，我们比较了小鼠间充质干细胞在大鼠肝脏生物基质支架和存在和不存在生长因子（GF）的二维底物中的细胞增殖和肝脏分化。在没有或存在GF的情况下，动态培养支架（DCS）刺激MSCs表达与功能改善相关的内胚层和肝细胞特异性基因和蛋白，细胞表现出成熟肝细胞的超微结构特征。当移植到ccl4损伤小鼠体内时，经DCS和GF联合预处理的细胞表现出更高的存活率、肝功能、植入宿主肝脏和进一步的肝分化。移植细胞对肝星状细胞和天然肝细胞的旁分泌作用在肝脏病理治疗中起关键作用。这些研究确定了一种有效的方法，可以促进具有广泛功能的间充质干细胞的肝脏分化，并支持进一步研究将脱细胞肝基质作为肝组织工程的生物支架。(C) 2012 Elsevier Ltd.版权所有。
Hepatocytes derived from mesenchymal stem cells (MSCs) hold great potential for cell-based therapies for liver diseases. The cell-based therapies are critically dependent on the hepatic differentiation of the MSCs with a high efficiency and on a considerable scale. Recent results have shown that decellularized organs provide a three-dimensional extracellular matrix for the lineage restriction of stem cell maturation. In this study, we compared the cell proliferation and hepatic differentiation of murine MSCs in a biomatrix scaffold from rat liver and in the presence and absence growth factors (GF) with a two-dimensional substrate. In the absence or presence of GF, the dynamic cultured scaffold (DCS) stimulated the MSCs to express endodermal and hepatocyte-specific genes and proteins associated with improved functions, and the cells exhibited the ultrastructural characteristics of mature hepatocytes. When transplanted into CCl4-injured mice, the cells pretreated with a combination of the DCS and GF exhibited increased survival, liver function, engraftment into the host liver and further hepatic differentiation. The paracrine effect of the transplanted cells on hepatic stellate cells and native hepatocytes played a key role in the treatment of the liver pathology. These studies define an effective method that facilitates the hepatic differentiation of MSCs exhibiting extensive functions and support further research into the use of a decellularized liver matrix as a bioscaffold for liver tissue engineering. (C) 2012 Elsevier Ltd. All rights reserved.