In vitro transdifferentiation of adult hematopoietic stem cells: An alternative source of engraftable hepatocytes
In vitro transdifferentiation of adult hematopoietic stem cells: An alternative source of engraftable hepatocytes
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DOI：
10.1016/j.jhep.2008.05.019
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发表时间：
2008-12-01
影响因子：
25.7
通讯作者：
Mukhopadhyay, Asok
中科院分区：
文献类型：
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作者：
Khurana, Satish;Mukhopadhyay, Asok
背景/目的：我们试图建立一个体外模型，将造血干细胞（hsc）转分化为移植到健康肝脏中的功能性肝细胞。方法：利用细胞外基质成分和肝毒性物质损伤小鼠血清模拟肝脏再生微环境。分化后的肝细胞在肝脏特异性基因和蛋白表达方面进行了表征。超微结构检测细胞变化，细胞色素p450酶测定功能活性。通过免疫组化分析检查这些肝细胞在健康肝组织中的可移植性。结果：一个特定的骨髓源性细胞亚群转分化为肝细胞，基因和蛋白的表达证实了这一点。分化后的细胞功能活跃，超微结构上微绒毛和其他细胞器的形成与原代肝细胞相似。在健康肝脏中，这些细胞移植到肝细胞板中并维持白蛋白和细胞角蛋白-18的表达。结论：肝培养系统可将造血干细胞分化为可移植于健康肝脏的功能性肝细胞。这一发现为使用自体骨髓细胞治疗许多肝脏疾病提供了另一种策略，从而避免了免疫抑制药物。(C) 2008年欧洲肝脏研究协会。Elsevier B.V.版权所有。
Background/Aims: We attempted to establish an ex vivo model for transdifferentiation of hematopoietic stem cells (HSCs) into functional hepatocytes for transplantation into healthy liver.Methods: We mimicked the liver regenerating microenvironment in culture by incorporating extracellular matrix components and sera obtained from mice with liver damaged by a hepatotoxic chemical. The differentiated hepatic cells were characterized in terms of liver-specific gene and protein expression. Cellular changes were determined by examining ultrastructure, and the functional activity was confirmed by cytochrome p450 enzyme assay. The engraftability of these hepatic cells in healthy liver tissue was checked by immunohistochemical analysis.Results: A specific sub-population of bone marrow-derived cells transdifferentiated into hepatic cells, confirmed by the expression of genes and proteins. The differentiated cells were found functionally active and ultrastructurally similar to primary hepatocytes in terms of the formation of microvilli and other cellular organelles. In healthy liver, these cells engrafted into hepatocyte plates and maintained the expression of albumin and cytokeratin-18.Conclusions: Hepatic culture system differentiated HSCs into functional hepatocytes, which were engraftable in healthy liver. This finding offers an alternative strategy for treating many liver ailments using autologous bone marrow cells, hence avoiding immuno-suppressive drugs. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.