ScholarWorks@성균관대학교

초록

Background: We had previously established an adequate cryopreservation process for hepatocyte spheroids for the development of an off-the-shelf bioartificial liver (BAL) system. The purpose of this study is to evaluate the efficacy of a BAL system containing cryopreserved immobilized porcine hepatocyte spheroids in a porcine model of acute liver failure (ALF). Methods: ALF pigs were divided into three groups. The control group consisted of treatment-na & iuml;ve pigs (n = 5), the blank group consisted of pigs that were attached to the BAL system not containing hepatocyte spheroids for 12 h (n = 5), and the BAL group consisted of pigs that were attached to the BAL containing hepatocyte spheroids for 12 h (n = 5). Results: Analysis of specific oxygen uptake rates showed that the hepatocytes sustained vigorous activity throughout the 12-h period of BAL operation. Median survival time of pigs was 24.0 h in the BAL group, 17.0 h in the blank group, and 15.0 h in the control group. The BAL group showed significantly prolonged survival according to Kaplan-Meier survival analysis compared to the blank group (p = 0.04) and control group (p = 0.04). Serum ammonia levels were significantly increased in the blank group (p < 0.01) and control group (p < 0.01), compared to the BAL group during the treatment period of the porcine ALF models. Prothrombin time (PT) was significantly lower in the BAL group compared to the blank group (p = 0.04) and control group (p = 0.01). Conclusions: A BAL system with a bioreactor containing cryopreserved immobilized hepatocyte spheroids showed effective clearance of serum ammonia, preservation of renal function, and improved survival in a porcine model of ALF.

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