Transplantation of human adipose stem cell-derived hepatocyte-like cells with restricted localization to liver using acellular amniotic membrane.
Transplantation of human adipose stem cell-derived hepatocyte-like cells with restricted localization to liver using acellular amniotic membrane.
复制标题
使用脱细胞羊膜移植限制性定位于肝脏的人脂肪干细胞衍生的肝细胞样细胞
DOI：
10.1186/s13287-015-0208-9
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发表时间：
2015-11-05
影响因子：
7.5
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Yuan J;Li W;Huang J;Guo X;Li X;Lu X;Huang X;Zhang H
成体干细胞源性肝细胞移植为临床个体化治疗肝衰竭或肝功能障碍提供了广阔的前景。然而，在这方面，肝细胞在肝脏疾病微环境中的低植入率一直是一个主要障碍。方法开发脱细胞人羊膜作为三维支架，并与来自人脂肪干细胞的肝细胞样细胞结合，以设计肝组织移植物，使肝细胞有效地植入肝脏。特异性基因表达和体外功能。当移植到肝脏的手术切口进行植入时，工程化肝移植物显著降低了四氯化碳治疗引起的肝损伤程度，并在移植后第3天在脱细胞人羊膜和受体肝脏之间产生了类似于肝脏中导管板的索。结论脱细胞人羊膜具有维持人脂肪干细胞来源的肝细胞样细胞功能表型的能力。功能性脱细胞人羊膜-肝细胞移植物与肝脏整合减轻小鼠急性肝损伤。这些工程化组织构建物可能支持基于干细胞的肝病个体化治疗和生物人工肝的建立。
IntroductionAdult stem cell-derived hepatocytes transplantation holds considerable promise for future clinical individualized therapy of liver failure or dysfunction. However, the low engraftment of the available hepatocytes in the liver disease microenvironment has been a major obstacle.MethodsAcellular human amniotic membrane was developed as a three-dimensional scaffold and combined with hepatocyte-like cells derived from human adipose stem cells to engineer a hepatic tissue graft that would allow hepatocyte engraftment in the liver effectively.ResultsThe hepatic tissue grafts maintained hepatocyte-specific gene expression and functionalityin vitro. When transplanted into the surgical incision in livers for engraftment, the engineered hepatic grafts significantly decreased the degree of liver injury caused by a carbon tetrachloride treatment and generated cords that were similar to the ductal plates in the liver between the acellular human amniotic membrane and the liver of receipts at day 3 post-transplantation. The hepatic tissue grafts maintained the expression of human hepatocyte-specific markers albumin, hepatocyte nuclear factor 4α, and cytochrome P450 2B6 in the liver of receipts, and acquired human-specific drug metabolism ability at eight weeks post-transplantation.ConclusionsThe acellular human amniotic membrane has the ability to maintain the functional phenotype of the hepatocyte-like cells derived from human adipose stem cells. Functional acellular human amniotic membrane-hepatocytes grafts integrated with the liver decreases the acute liver injury of mice. These engineered tissue constructs may support stem cell-based individualized therapy for liver disease and for bioartificial liver establishment.