Performance of plasma-perfused, microencapsulated hepatocytes: prospects for extracorporeal liver support.
The growing success of liver transplantation and the shortage of donor livers has turned attention to the possibility of utilizing hepatocytes within artificial liver support systems to allow time for donor livers to become available and to improve the condition of patients with hepatic failure. This study evaluated encapsulated hepatocytes, a technology which might allow the possibility of using xenogenic or human hepatoma cells. Rabbit hepatocytes were encapsulated using the ionic polysaccharides carboxymethylcellulose, chondroitin sulfate A, chitosan, and polygalacturonic acid. Encapsulated cells were maintained in perfusion culture for at least 6 days in heparinized, normal human plasma or in a defined culture medium. Parallel cultures of plated hepatocytes were also conducted. The metabolic capability of the cells was evaluated by following the rates of urea, albumin, and transferrin synthesis and the transformation rate of the drug antipyrine. Protein synthesis and ureogenesis in plasma were depressed from the levels expressed in defined culture medium. Drug detoxification as measured by antipyrine metabolism appeared to be enhanced in plasma. We conclude that encapsulated rabbit hepatocytes retain significant levels of function for at least 6 days of perfusion with human plasma, suggesting the feasibility of this technology as a potential method of short-term liver support.
Matthew
H W
HW
Department of Chemical Engineering, Wayne State University, Detroit, MI.
Basu
S
S
Peterson
W D
WD
Salley
S O
SO
Klein
M D
MD
D000418:Albumins / Q000378:metabolism; D000818:Animals; D000983:Antipyrine / Q000378:metabolism; D002266:Carboxymethylcellulose Sodium; D002478:Cells, Cultured; D002686:Chitin / Q000031:analogs & derivatives; D048271:Chitosan; D002809:Chondroitin Sulfates; D003470:Culture Media; D004339:Drug Compounding / Q000379:methods*; D005112:Extracorporeal Circulation / Q000379:methods*; D005240:Feasibility Studies; D006490:Hemostatics; D006493:Heparin; D006801:Humans; D008099:Liver / Q000166:cytology* / Q000378:metabolism; D017114:Liver Failure, Acute / Q000628:therapy*; D008297:Male; D010368:Pectins; D010949:Plasma; D011817:Rabbits; D013997:Time Factors; D014168:Transferrin / Q000378:metabolism; D014508:Urea / Q000378:metabolism
D000418:Albumins; D003470:Culture Media; D006490:Hemostatics; D014168:Transferrin; D002686:Chitin; D010368:Pectins; D014508:Urea; D006493:Heparin; D002809:Chondroitin Sulfates; D048271:Chitosan; D002266:Carboxymethylcellulose Sodium; D000983:Antipyrine; C003181:polygalacturonic acid