Homogeneous differentiation of hepatocyte-like cells from embryonic stem cells: applications for the treatment of liver failure
Homogeneous differentiation of hepatocyte-like cells from embryonic stem cells: applications for the treatment of liver failure
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DOI：
10.1096/fj.06-7764com
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发表时间：
2008-03-01
期刊：
影响因子：
4.8
通讯作者：
Yarmush, Martin L.
中科院分区：
文献类型：
--
作者：
Cho, Cheul H.;Parashurama, Natesh;Yarmush, Martin L.
用于治疗肝衰竭的细胞疗法的主要障碍之一是功能性人肝细胞的低可用性。虽然胚胎干（ES）细胞代表了用于治疗的潜在细胞来源，但目前的分化方法导致混合的细胞群或目的细胞的低产量。在这里，我们描述了一种快速，直接分化的方法，产生一个均匀的人口内胚层样细胞的纯度为95%。小鼠ES细胞在胶原蛋白夹心肝细胞上培养，分化并增殖成均匀和同质的内胚层样细胞的细胞群。内胚层样细胞群对Foxa 2、Sox 17和AFP呈阳性，并可进一步分化为肝细胞样细胞，证明了肝脏形态、功能以及基因和蛋白表达。将肝细胞样细胞移植到生物人工肝装置中以治疗暴发性肝功能衰竭，提高了动物的存活率，从而强调了这些细胞的治疗潜力。乔角，澳-地H、Parashurama，N.，帕克河，加-地Y. H、Sugamuna，K，Nahoun，Y.，帕克，J.，Tilles，A. W.，Berthiaume，F.，雅穆什，M。L.胚胎干细胞向肝细胞样细胞的同质分化：在肝衰竭治疗中的应用。
One of the major hurdles of cellular therapies for the treatment of liver failure is the low availability of functional human hepatocytes. While embryonic stem (ES) cells represent a potential cell source for therapy, current methods for differentiation result in mixed cell populations or low yields of the cells of interest. Here we describe a rapid, direct differentiation method that yields a homogeneous population of endoderm-like cells with 95% purity. Mouse ES cells cultured on top of collagen-sandwiched hepatocytes differentiated and proliferated into a uniform and homogeneous cell population of endoderm-like cells. The endoderm-like cell population was positive for Foxa2, Sox17, and AFP and could be further differentiated into hepatocyte-like cells, demonstrating hepatic morphology, functionality, and gene and protein expression. Incorporating the hepatocyte-like cells into a bioartificial liver device to treat fulminant hepatic failure improved animal survival, thereby underscoring the therapeutic potential of these cells.-Cho, C. H., Parashurama, N., Park, E. Y. H., Sugamuna, K, Nahmias, Y., Park, J., Tilles, A. W., Berthiaume, F., Yarmush, M. L. Homogeneous differentiation of hepatocyte-like cells from embryonic stem cells: applications for the treatment of liver failure.