Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China.
Biomaterials. 2012 Dec;33(35):8995-9008. doi: 10.1016/j.biomaterials.2012.08.058. Epub 2012 Sep 15.
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 CCl(4)-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.
由间充质干细胞（MSCs）衍生而来的肝细胞在基于细胞的肝脏疾病治疗中具有巨大的潜力。基于细胞的治疗方法极大地依赖于 MSCs 的高效和相当规模的肝分化。最近的结果表明，去细胞化的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，我们比较了鼠源 MSCs 在大鼠肝生物基质支架中的细胞增殖和肝分化，以及有无生长因子（GF）的二维基质。在有无 GF 的情况下，动态培养支架（DCS）刺激 MSCs 表达内胚层和肝细胞特异性基因和蛋白，与改善功能相关，并且细胞表现出成熟肝细胞的超微结构特征。当移植到 CCl4 损伤的小鼠中时，用 DCS 和 GF 的组合预处理的细胞表现出增加的存活率、肝功能、向宿主肝脏的植入和进一步的肝分化。移植细胞对肝星状细胞和固有肝细胞的旁分泌作用在肝脏病理学的治疗中发挥了关键作用。这些研究定义了一种有效的方法，促进了具有广泛功能的 MSCs 的肝分化，并支持进一步研究使用去细胞化的肝基质作为肝脏组织工程的生物支架。
