Construction of Liver Tissue in vivo with Preparative Partial Hepatic Irradiation and Growth Stimulus: Investigations of Less Invasive Techniques and Progenitor Cells
Construction of Liver Tissue in vivo with Preparative Partial Hepatic Irradiation and Growth Stimulus: Investigations of Less Invasive Techniques and Progenitor Cells
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通过制备性部分肝照射和生长刺激构建体内肝组织：微创技术和祖细胞的研究
DOI：
10.1016/j.jss.2013.06.016
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发表时间：
2013
影响因子：
2.2
通讯作者：
and Susumu Eguchi
中科院分区：
文献类型：
--
作者：
Kensuke Miyazaki;Kosho Yamanouchi;Yusuke Sakai;Izumi Yamaguchi;Mitsuhisa Takatsuki;Tamotsu Kuroki;Chandan Guha;and Susumu Eguchi
背景肝移植肝细胞的选择性增殖与生长刺激，如肝部分切除或肝细胞生长因子，伴随肝照射（HIR），可以抑制宿主肝细胞的增殖，已被报道。我们已经进行了实验，专注于微创和临床适用的技术和progenitor cells.Materials and MethodsFirst，二肽基肽酶IV-F344或黄疸古恩大鼠进行部分HIR（只有30%的全肝）和门静脉分支结扎（PVBL）的一个叶，然后在1 × 107脾内肝细胞移植。其次，在部分HIR和PVBL后，移植两种类型的祖细胞（即，小肝细胞（SH）或脂肪来源的间充质干细胞。结果移植后16周，供体细胞构成> 70%的肝细胞的照射叶，显示连接蛋白32，磷酸烯醇式丙酮酸羧激酶-1，和糖原储存。此外，黄疸古恩大鼠的血清胆红素水平显著降低，并在整个24周的实验期间保持在该水平。SH的生长速度比肝细胞快。8周后，约40%的宿主肝细胞已被移植的SH所取代。虽然供体脂肪来源的间充质细胞移植后8周，其增殖没有observed.ConclusionsHIR，结合PVBL，可以给选择性肝叶，是一种微创，但有效的方法移植肝细胞增殖。即使是少量的SHs也能以其特有的增殖能力构建肝组织。
BackgroundThe selective proliferation of transplanted hepatocytes with a growth stimulus, such as partial hepatectomy or hepatocyte growth factor, concomitant with hepatic irradiation (HIR), which can suppress proliferation of host hepatocytes, has been reported. We have conducted experiments that focused on less invasive and clinically applicable techniques and progenitor cells.Materials and methodsFirst, dipeptidyl-peptidase IV-F344 or jaundiced Gunn rats underwent partial HIR (only 30% of whole liver) and portal vein branch ligation (PVBL) of one lobe, followed by intrasplenic hepatocyte transplantation at 1 × 107. Second, after partial HIR and PVBL, two types of progenitor cells were transplanted (i.e., small hepatocytes (SHs) or adipose-derived mesenchymal stem cells.ResultsSixteen weeks after transplantation, the donor cells constituted > 70% of the hepatocytes of the irradiated lobe, showing connexin 32, phosphoenolpyruvate carboxykinase-1, and glycogen storage. Moreover, the serum bilirubin level had decreased significantly in the jaundiced Gunn rats and remained at this level throughout the 24 wk experimental period. The SHs grew more quickly than the hepatocytes. After 8 wk, around 40% of the host hepatocytes had been replaced by transplanted SHs. Although the donor adipose-derived mesenchymal cells were engrafted after 8 wk, their proliferation was not observed.ConclusionsHIR, combined with PVBL, can be given to a selective liver lobe and is a less-invasive but effective method for proliferation of transplanted hepatocytes. Even a smaller number of SHs can construct liver tissue with their prevailing proliferative ability.