Experimental study of bioartificial liver with cultured human liver cells

Abstract

AIM:To establish an extracorporeal bioartificial liver support system (EBLSS) using cultured human liver cells and to study its support effect for fulminant hepatic failure (FHF).METHODS:The liver support experiment of EBLSS consisting of aggregates cultured human liver cells, hollow fiber bioreactor, and circulation unit was carried out in dizhepatic dogs.RESULTS:The viability of isolated hepatocytes and nonparenchymal liver cells reached 96%. These cells were successfully cultured as multicellular spheroids with synthetic technique. The typical morphological appearance was retained up to the end of the artificial liver experiment. Compared with the control dogs treated with EBLSS without liver cells, the survival time of artificial liver support dogs was significantly prolonged. The changes of blood pressure, heart rate and ECG were slow. Both serum ammonia and lactate levels were significantly lowered at the 3rd h and 5th h. In addition, a good viability of human liver cells was noted after 5h experiment.CONCLUSION:EBLSS playing a metabolic role of cultured human hepatocytes,is capable of compensating the function of the liver, and could provide effective artificial liver support and therapy for patients with FHF.

Figure 1

Multicellular spheroids of human hepatocytes and nonparenchymal liver cells. Phase-contrast microscope. × 400

Figure 2

Survival curve in the support and control groups.

Figure 3

Changes of serum ammonia in dizhepatic dogs.

Figure 4

Changes of serum lactate in dizhepatic dogs.