Transplantation of human hepatocytes

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      Initially autologous hepatocytes were isolated and reinfused in patients affected by end-stage cirrhosis, resulting in poor and extremely limited outcomes (Mito et al., 1992). Simultaneously, another group used allogenic donor cells to provide subsistence to patients with fulminant hepatitis (Strom et al., 1997). Such approach proved to be efficient and safe, since donor hepatocytes were able to provide support of metabolic and synthetic liver functions while the native liver regenerated.

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      The selective advantage for FAH+ hepatocytes also led to an FAH mouse with a “humanized” liver. An FRG immune deficient null mouse model, Fah−/−/Rag2−/−/IL2rg−/− was repopulated with human FAH+ hepatocytes [83, 84]. Even though the mouse has answered many questions and recapitulates many aspect of the human liver disease, there are limitations, and the model is missing a critical phenotype of the disease, cirrhosis.

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      Another study evaluated autologous transfers with some success as demonstrated by a reduction in ammonia levels. Unlike the other previously described conditions, A1AD with time leads to parenchymal damage, which complicates potential cell engraftment due to destruction of the innate liver structure.11 Other conditions that have been evaluated with similar results include glycogen storage diseases, urea cycle disorders, and factor VII deficiency.12,13

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