A novel approach to ex vivo gene therapy for familial hypercholesterolemiausing human amniotic epithelial cells as a transgene carrier

This study has demonstrated the potential of human amniotic epithelial cell s (HAEC) as a transgene carrier to treat patients with familial hypercholes terolemia (FH). One approach to liver-directed gene therapy is represented by transplantation of autologous hepatocytes that have been genetically mod ified in vitro. However, the hepatocytes must be isolated from surgically r esected tissue and it is difficult to expand the hepatocytes in culture. In contrast, the advantages for using HAEC are the higher availability and th e nonimmunogenicity after allotransplantation. Our strategy involved isolat ing HAEC from an amnion, transducing a human low-density lipoprotein recept or (LDLR) gene into these cells with a recombinant adenovirus, and transpla nting the genetically modified cells into the liver of an animal model of P H. Each animal, treated with the LDLR-transduced HAEC, exhibited a substant ial decrease in serum cholesterol with an eventual return to pretreatment l evel. Moreover, the transplanted HAEC) migrated out of the sinusoids into t he hepatic parenchyma and expressed the LDLRs until at least 20 days after transplantation. However, the transplanted HAEC markedly decreased in numbe r after 10 days post-transplant with an increase of inflammatory cells. The temporary nature of the metabolic improvement may be associated with xenog raft rejection and transient function of the adenoviral vector. (C) 2001 To hoku University Medical Press.