The significant improvement of survival times and pathological parameters by bioartificial liver with recombinant HepG2 in porcine liver failure model.
We developed a bioartificial liver (BAL) containing human hepatoblastoma cell line, HepG2, with the addition of ammonia removal activity by transfecting a glutamine synthetase (GS) gene and estimated the efficacy using pigs with ischemic liver failure. GS-HepG2 cells showed 15% ammonia removal activity of porcine hepatocytes, while unmodified HepG2 had no such activity. The established GS-HepG2 cells were grown in a circulatory flow bioreactor to 3.5-4.1 x 10(9) cells. Survival time of the animals treated with GS-HepG2 BAL was significantly prolonged compared to the cell-free control (14.52 +/- 5.24 h vs. 8.53 +/- 2.52 h) and the group treated with the BAL consisting of unmodified wild-type HepG2 (9.58 +/- 4.52 h). Comparison showed the cell-containing BAL groups to have significantly fewer incidences of increased brain pressure. Thus, the GS-HepG2 BAL treatment resulted in a significant improvement of survival time and pathological parameters in pigs with ischemic liver failure.
Enosawa
Shin
S
Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan. senosawa@nch.go.jp
Miyashita
Tomoyuki
T
Saito
Tomohiro
T
Omasa
Takeshi
T
Matsumura
Toshiharu
T
D000818:Animals; D019149:Bioreactors; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D017690:Cell Transplantation; D006224:Cricetinae; D004195:Disease Models, Animal; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017093:Liver Failure / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D019164:Liver, Artificial; D008297:Male; D008954:Models, Biological; D015996:Survival Rate; D013552:Swine; D014162:Transfection
D005974:Glutamate-Ammonia Ligase