Effective hepatocyte transplantation using rat hepatocytes with low asialoglycoprotein receptor expression
Effective hepatocyte transplantation using rat hepatocytes with low asialoglycoprotein receptor expression
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DOI：
10.1016/s0002-9440(10)63315-9
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发表时间：
2004-08-01
影响因子：
6
通讯作者：
Ikeda, U
中科院分区：
文献类型：
--
作者：
Ise, H;Nikaido, T;Ikeda, U
开发一种可靠的分离高增殖潜能肝细胞的方法为肝细胞移植领域的进展提供了至关重要的信息。本研究的目的是根据肝细胞移植的去唾液酸糖蛋白受体（ASGPR）表达水平，使用高度增殖的祖细胞样肝细胞开发可靠的肝细胞移植。我们以前曾报道，小鼠肝细胞与低ASGPR表达水平具有高度的增殖潜力，可以用作祖细胞样肝细胞。因此，我们将表达低水平和高水平ASGPR的F344雄性大鼠肝细胞分级，并根据肝脏中低水平和高水平ASGPR表达确定肝细胞的肝脏再增殖能力。接下来，将每种类型的2 x 10（5）个细胞移植到雌性肝脏再生模型二肽基肽酶缺陷大鼠中，我们通过识别Y染色体上的Sry基因来估计宿主肝脏中移植肝细胞的肝脏再增殖率。肝细胞移植后60 d，低ASGPR表达组移植肝细胞占肝细胞总量的76%，而高ASGPR表达组和未分级肝细胞移植肝细胞分别占肝细胞总量的12%和17%。总之，这些发现表明，低ASGPR表达肝细胞可导致正常肝功能和体内高再增殖能力。这些结果提供了深入了解的发展策略，有效的肝细胞移植肝细胞的再增殖。
Development of a reliable method of isolating highly proliferative potential hepatocytes provides information crucial to progress in the field of hepatocyte transplantation. The aim of this study was to develop reliable hepatocyte transplantation using highly proliferative, eg, progenitor-like hepatocytes, based on asialoglycoprotein receptor (ASGPR) expression levels for hepatocyte transplantation. We have previously reported that mouse hepatocytes with low ASGPR expression levels have highly proliferative potential and can be used as progenitor-like hepatocytes. We therefore fractionated F344 male rat hepatocytes expressing low and high levels of ASGPR and determined the liver repopulation capacity of hepatocytes according to low and high ASGPR expression in the liver. Next, 2 x 10(5) cells of each type were transplanted into female liver regenerative model dipeptidyl peptidase-deficient rats, and we estimated the rate of liver repopulation by the transplanted hepatocytes in the host liver, as determined by recognition of the Sry gene on the Y-chromosome. At 60 days after hepatocyte transplantation, the transplanted hepatocytes occupied similar to76% of the total hepatocyte mass in the case of the transplantation of hepatocytes with low ASGPR expression, but accounted for similar to12% and 17% of the mass in the case of the transplantation of hepatocytes with high ASGPR expression and unfractionated hepatocytes, respectively. in conclusion, these findings suggest that hepatocytes with low ASGPR expression can result in normal liver function and a high repopulation capacity in vivo. These results provide insight into development of a strategy for effective liver repopulation using transplanted hepatocytes.