Metabolic disorders of the liver manifest in a large number of ways, and have an equally wide spread of impact on an afflicted patients life. Many different avenues for treatment are under investigation, including direct administration of the deficient protein or cofactor, replacement of the aberrant gene by way of viral vectors, and even stem cell repopulation of the target organ. The highly regenerative nature of the liver provides more benefit than hindrance for investigations on potential curative therapies. Still, this deceptively complex organ is merely a part of an extremely intricate whole organism; thus the organism, the disease, and the proposed treatment must all be understood completely before there is hope for releasing a safe and effective cure.

Of the many liver metabolic disorders in existence, those most conducive to novel curative strategies tend to be of simple, well-characterized monogenic origin. The animal models of two such disorders were evaluated for their basic potential to benefit from combination ex vivo engineered stem cell therapy. The hyperbilirubinemic Gunn rat model of Crigler Najjar Syndrome was initially examined for hepatic reconstitution capacity from various cell infusions. We discovered that the therapeutic index for monocrotaline, administered to potentiate infused cell repopulation, is too small for practical use in this model. This finding is important for future investigations of the model, indicating the use of the more costly alternative, retrorsine.

The hypoglycemic mouse model of Glycogen Storage Disease type 1a (von Geirke’s disease) was also investigated for potential gains with novel treatment.