Ueda Yuichiro, Iwata Hiroo, Paek Hyun Joon, Ko In Kap, Shimooka Yutaka, Katsura Nagato, Ikai Iwao, Yamaoka Yoshio, Ikada Yoshito
Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
ASAIO J. 2003 Jul-Aug;49(4):401-6.
In our series of studies, we have made an effort to develop a bioartificial liver (BAL) system through which whole blood can be perfused as in hemodialysis therapy. In this study, BAL cartridges containing porcine hepatocytes were prepared and perfused in an extracapillary space with human whole blood in vitro. Lidocaine loading tests were performed to evaluate the detoxification ability of the BAL. The clearance value of lidocaine decreased during the initial 6 hours to about 50% of the initial value. After that, it was almost stable until 48 hours. After 48 hours perfusion, thin sections of the hollow fibers containing hepatocytes were prepared and stained with hematoxylin-eosin and immunohistochemically stained for membrane attack complex (MAC). The porcine hepatocytes formed aggregates in the hollow fibers, nuclei in the cells were observed clearly, and MAC was not seen on the porcine hepatocyte aggregation. A hollow fiber that can reject 90% of molecules with molecular weight of 50 kDa effectively protects porcine hepatocytes from humoral immunity. The in vivo assessment of the BAL cartridge was performed using a canine model for 24 hours. No significant hemolysis or thrombus that affected the BAL system and the canine were observed. These results suggest that our BAL system is a promising liver assist device through which patients' whole blood can be perfused.
在我们的系列研究中，我们致力于开发一种生物人工肝（BAL）系统，通过该系统可以像血液透析治疗一样灌注全血。在本研究中，制备了含有猪肝细胞的BAL柱，并在体外将人全血在毛细血管外空间进行灌注。进行利多卡因负荷试验以评估BAL的解毒能力。利多卡因的清除值在最初6小时内降至初始值的约50%。此后，直到48小时几乎保持稳定。在灌注48小时后，制备含有肝细胞的中空纤维薄片，用苏木精-伊红染色，并进行膜攻击复合物（MAC）免疫组织化学染色。猪肝细胞在中空纤维中形成聚集体，细胞中的细胞核清晰可见，在猪肝细胞聚集体上未观察到MAC。一种能够有效排斥90%分子量为50 kDa分子的中空纤维可有效保护猪肝细胞免受体液免疫。使用犬模型对BAL柱进行了24小时的体内评估。未观察到影响BAL系统和犬的明显溶血或血栓形成。这些结果表明，我们的BAL系统是一种有前景的肝辅助装置，通过该装置可以灌注患者的全血。
