Repeated Transplantation of Microencapsulated Hepatocytes for Sustained Correction of Hyperbilirubinemia in Gunn Rats

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Abstract
In previous studies we demonstrated that transplantation of microencapsulated hepatocytes could correct congenital hyperbilirubinemia in Gunn rats for 4 to 6 wks. Reduction in hyperbilirubinemia followed a single transplantation of isolated encapsulated hepatocytes (IEH). After 4 to 6 wks of transplantation IEH gradually lose their functionality. To sustain long-term supplementation of liver function we have investigated the efficacy of monthly IEH transplantations for 6 mo. Hepatocytes, isolated from young Wistar rats, were microencapsulated with a collagen matrix within an alginate-poly L-lysine composite membrane. We transplanted IEH intraperitoneally into homozygous Gunn rats at monthly (4-wk) intervals for 6 mo. Control Gunn rats received intraperitoneal transplantations of empty microcapsules. Total serum bilirubin was measured in the IEH-transplanted and control Gunn rats at weekly intervals for the duration of the 6-month study. A significant (p < 0.01) and sustained decrease (by nearly 50%) in total serum bilirubin levels was observed following monthly IEH transplantations in Gunn rats for the duration of the study. No such decrease in total serum bilirubin levels was seen in the controls. The Gunn rats exhibited good tolerance for the multiple IEH transplantations. Thus, repeated IEH transplantations may be one strategy for providing long-term supplementation of liver function in congenital metabolic liver disease.