In vitro evaluation of metabolic functions of a bioartificial liver
In vitro evaluation of metabolic functions of a bioartificial liver
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DOI：
10.1097/00002480-199907000-00009
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发表时间：
1999-07-01
期刊：
影响因子：
4.2
通讯作者：
Ikada, Y
中科院分区：
文献类型：
--
作者：
Iwata, H;Sajiki, T;Ikada, Y
本研究的目的是开发一种结构简单的生物人工肝（BAL），可以在几个小时内制备出来，并且可以像现有的血液透析器一样灌注全血。从 37 头猪中分离出肝细胞；每个肝脏重300至400克。每个肝脏的肝细胞平均产量为 2.4 +/- 0.6 x 10(10) 个细胞，细胞活力为 89.6 +/- 3.9%。为了制备 BAL 装置，使用了由二乙酸纤维素制成的中空纤维组成的筒。中空纤维的标称截留分子量为68kDa，内径为195μm。将100毫升含1×10(10)个细胞的肝细胞悬液接种到中空纤维的内部空间，并关闭中空纤维盒的入口和出口。从对猪进行麻醉到开始对制备的 BAL 装置进行体外评估仅用了 3 小时。为了定量评估该 BAL 的功能，使用药代动力学方法，将新鲜人血和 Dulbecco 改良 Eagle 培养基的混合物以 200 ml/min 的速度在中空纤维的壳空间中循环。然后将化学物质（利多卡因、氨和半乳糖）加载到灌注介质中。发现 BAL 装置的平均固有清除率对于利多卡因为 46 毫升/分钟，对于氨为 8.8 毫升/分钟。 BAL 装置的半乳糖消除能力为 1.34 mg/min。体外循环10天后，BAL装置对利多卡因、氨和半乳糖的代谢功能分别比初始功能下降81%、49%和64%。
The purpose of this study is to develop a bioartificial liver (BAL) with such a simple structure that it can be prepared within several hours and through which whole blood can be perfused as in current hemodialyzers. Hepatocytes were isolated from 37 pigs; each liver weighed 300 to 400 g. The average yield of hepatocytes was 2.4 +/- 0.6 x 10(10) cells per liver, with a cell viability of 89.6 +/- 3.9%. To prepare a BAL device, a cartridge, composed of hollow fibers made of cellulose diacetate was used. Nominal cut-off molecular weight of the hollow fibers was 68 kDa, and the internal diameter was 195 mu m. One hundred milliliters of hepatocyte suspension, containing 1 x 10(10) cells, was inoculated into the inner space of the hollow fibers, and both the inlet and outlet of the hollow fiber cartridge were closed. It took only 3 hrs from administration of the pig's anesthesia to the start of an in vitro evaluation of the prepared BAL device. To evaluate the functions of this BAL quantitatively, using a pharmacokinetic method, a mixture of fresh human blood and Dulbecco's modified Eagle medium was circulated in the shell space of the hollow fibers at 200 ml/min. Chemicals (lidocaine, ammonia, and galactose) were then loaded into the perfusion medium. The average intrinsic clearance of the BAL device was found to be 46 ml/min for lidocaine and 8.8 ml/min for ammonia. The galactose elimination capacity of the BAL device was 1.34 mg/min. The metabolic function of the BAL device decreased by 81%, 49%, and 64% of the initial function for lidocaine, ammonia, and galactose, respectively, after 10 days of in vitro circulation.