Improvement of the survival rate by fetal liver cell transplantation in a mice lethal liver failure model
Improvement of the survival rate by fetal liver cell transplantation in a mice lethal liver failure model
复制标题
DOI：
10.1097/01.tp.0000287967.54222.4d
复制
发表时间：
2007-11-27
期刊：
影响因子：
6.2
通讯作者：
Ikai, Iwao
中科院分区：
文献类型：
--
作者：
Machimoto, Takafumi;Yasuchika, Kentaro;Ikai, Iwao
背景资料。由于供体长期短缺，细胞移植作为原位肝移植的一种替代疗法已被广泛预期。我们以前曾报道过一种方法，用来丰富形成细胞聚集的肝祖细胞(HPC)。在本研究中，我们将HPC移植到肝损伤模型小鼠体内，以确定HPC移植是否可以改善肝功能障碍。我们从绿色荧光蛋白(GFP)转基因小鼠的E13.5胎肝中获得供体细胞。我们将GFP阳性胎肝细胞移植到白蛋白增强子/启动子控制下表达白喉毒素(DT)受体的转基因小鼠体内。随后，我们通过给予DT对受体小鼠造成选择性肝损伤。然后，我们评估了移植细胞的植入及其对生存的影响。低剂量DT可致小鼠亚致死性肝损伤，高剂量DT可致肝损伤模型小鼠致死。移植的GFP阳性细胞被移植到受体肝脏并表达白蛋白，类似于成熟的肝细胞。它们继续扩散，形成集群。细胞移植组移植后25d存活率(40.0%，8/20)明显高于假手术组(0/20，0%)，差异有统计学意义(P=0.0047)。将移植的细胞植入受体小鼠的肝脏并重新填充，提高了肝损伤模型小鼠的存活率。因此，我们认为HPC是一种理想的细胞移植来源。
Background. The use of cell transplantation as an alternative therapy for orthotopic liver transplantation has been widely anticipated due to a chronic donor shortage. We previously reported the method used to enrich hepatic progenitor cells (HPCs) forming cell aggregations. In this study, we transplanted HPCs into the liver injury model mice to determine whether HPC transplantation may improve the liver dysfunction.Methods. We obtained donor cells from E13.5 fetal livers of green fluorescent protein (GFP) transgenic mice. We transplanted GFP-positive fetal liver cells into the transgenic mice which express diphtheria toxin (DT) receptors under the control of an albumin enhancer/promoter. Subsequently, we induced selective liver injury to recipient mice by DT administration. We then evaluated the engraftment of the transplanted cells and their effect on survivorship.Results. The low dose of DT induced sublethal liver injury and the high dose of DT was lethal to the liver injury model mice. The transplanted GFP-positive cells were engrafted into the recipient livers and expressed albumin, resembling mature hepatocytes. They continued to proliferate, forming clusters. The survival rate at 25 days after transplantation of the cell -transplanted group (8 of 20; 40.0%) was improved significantly (P=0.0047) in comparison to that of the sham-operated group (0 of 20; 0%).Conclusions. The transplanted cells were engrafted and repopulated the liver of recipient mice, resulting in the improvement of the survival rate of the liver injury model mice. We therefore propose that HPCs are a desirable cell source for cell transplantation.