Hepatocyte organoid culture in elliptic hollow fibers to develop a hybrid artificial liver.
Hepatocyte organoid culture in elliptic hollow fibers to develop a hybrid artificial liver.
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在椭圆形中空纤维中培养肝细胞类器官，以开发混合型人工肝。
DOI：
10.5301/ijao.2008.5566
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
K. Funatsu
中科院分区：
文献类型：
--
作者：
J. Fukuda;H. Mizumoto;K. Nakazawa;T. Kajiwara;K. Funatsu
开发了一种新的类器官培养物，其中肝细胞在体外维持高肝功能数周以上。组织工程类器官的主要缺点是聚集的细胞之间缺乏血管结构。由于氧的耗尽，肝细胞可以存活的类器官表面的厚度是有限的。该研究表明，通过在中空纤维（HF）中使用离心力形成的大鼠肝细胞类器官具有距类器官表面约80 - 100微米的存活极限厚度。在此基础上，我们用一种简单的退火方法设计了一种小直径小于150 μ m的椭圆形HF。所有的肝细胞提供氧气，并形成一个类器官没有死细胞层，在这个HF一个肝细胞类器官在椭圆形HF保持氨去除活性的两倍，在原始HF至少一个月的培养过程中。椭圆形HF中的类器官的白蛋白分泌活性也维持至少一个月，并且与活体中的肝脏的白蛋白分泌活性处于相同水平。总之，利用椭圆形HF培养类器官似乎是一种很有前途的技术，以开发一个混合型人工肝。
A novel organoid culture was developed in which hepatocytes maintain high liver functions for more than several weeks in vitro. The main disadvantage of tissue-engineered organoids is the lack of a blood vessel structure between the aggregated cells. Because of depletion of oxygen, the thickness from the surface of an organoid at which hepatocytes can survive is limited. This study showed that a rat hepatocyte organoid that forms by using centrifugal force in a hollow fiber (HF) had a survival limit thickness of about 80 - 100 microm from the surface of the organoid. Based on the value, we designed an elliptic HF having less than 150 microm minor diameter by using a simple annealing method. All hepatocytes were supplied with oxygen and formed an organoid without a dead cell layer in this HF A hepatocyte organoid in an elliptic HF maintained ammonia removal activity twice as high as in the original HF for at least one month during culture. Albumin secretion activity of an organoid in an elliptic HF was also maintained for at least one month and was the same level as that of liver in a living body. In conclusion, organoid culture by using an elliptic HF seems to be a promising technique to develop a hybrid artificial liver.