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H Matsue

Publications and source records attributed to H Matsue.

76 records · Page 5Linked to original sources

Does a porcine hepatocyte hybrid artificial liver prolong the survival time of anhepatic rabbits?

To examine cultured porcine hepatocytes as a bioreactor of a hybrid artificial liver (HAL) in rabbits, a small version of a multiplated HAL was manufactured. In vitro and ex vivo studies were performed to evaluate the small HAL. The HAL consisted of 50 glass plates (10 x 5 x 0.04 cm each) on which porcine hepatocytes were cultured in a monolayer at confluent cell density. After 2 days of standard cultivation, the glass plates with hepatocytes were placed in the module and were used for studies. The module contains about 5 grams of hepatocytes (1/10 of 2 kg.bw rabbit liver). After undergoing perfusion culture for 5 days, the HAL showed satisfactory hepatic function. Glucose and urea were synthesized at the rate of 4.06 +/- 0.7 mg/module/hr and 0.62 +/- 0.09 mg/module/hr, respectively, and loaded ammonia was metabolized at the rate of 1.29 +/- 0.26 mg/module/hr. Ex vivo extracorporeal plasma perfusion studies revealed that the module with cultured porcine hepatocytes, which were heterogeneous to rabbits, showed a tendency to prolong the survival time of anhepatic rabbits. These results indicate that the HAL system, using multiplated porcine hepatocyte monolayers, is a promising artificial liver support system for clinical cases.

Animals↗

A hybrid artificial liver system. Function of cultured monolayer pig hepatocytes in plasma from hepatic failure patients.

To produce a new hybrid artificial liver system, cultured pig hepatocytes were used in this study. Hepatocytes from normal healthy pigs were cultured in multiwell dishes. From the third day of cultivation, hepatocytes were divided into three groups according to the media used (Group 1, L-15; Group 2, normal human plasma; Group 3, plasma from hepatic failure [HF] patients). Measurements of cellular function of the cultured pig hepatocytes included metabolic activity (gluconeogenesis and ureogenesis), DNA content, and amino acid changes in the plasma. The ability to provide gluconeogenesis and ureogenesis by the cultured hepatocytes in HF plasma was maintained for 3 days, equal to that observed in Groups 1 and 2. DNA content was no different in the three groups. Elevated amino acid levels in the HF plasma, Phe, Met, Lys, and Gly, were significantly reduced by the cultured hepatocytes. The results indicate that the use of primary cultured pig hepatocytes is a step toward a hybrid artificial liver system, and a promising candidate as a bioreactor.

Amino Acids↗

Immunologic considerations in the use of cultured porcine hepatocytes as a hybrid artificial liver. Anti-porcine hepatocyte human serum.

Cultured porcine hepatocytes with reasonable metabolic functions are a promising bioreactor for a hybrid artificial liver in the treatment of liver failure. A cytotoxic human serum (t-serum) against cultured porcine hepatocytes was accidentally discovered during preliminary experiments, however, which prompted the authors to study the mechanism of the cytotoxicity and the frequency of occurrence of the cytotoxic sera. Among 103 individual sera examined, seven (6.8%) sera showed cytotoxicity to cultured porcine hepatocytes. T-serum heated at 56 degrees C for 30 min completely lost its cytotoxic activity, but the inactivated cytotoxicity was restored by the addition of rabbit complement to the inactivated t-serum. IgM-depleted t-serum produced by 2-mercaptoethanol treatment abolished the cytotoxicity to porcine hepatocytes. The cytotoxic reactions were therefore thought to be mediated by IgM capable of complement activation. Although IgM binding to porcine hepatocytes was also seen in nontoxic sera, the IgM did not activate complement. This implies differences in hepatocyte surface antigens recognized by IgM from t- and nontoxic sera. Before clinical application of a hybrid artificial liver using cultured porcine hepatocytes, detection of cytotoxic human IgM against porcine hepatocytes is necessary, and the means of eliminating the cytotoxic IgM from the hybrid artificial liver system, or of inactivating complement in the system, will be desirable in cases positive for cytotoxic IgM.

Adult↗