Ej. Kremer et al., ADENOVIRUS VECTOR-TRANSDUCED HEPATOCYTES IMPLANTED VIA A PREFORMED COLLAGEN PTFE SUPPORT PERSIST FOR AT LEAST 4 WEEKS IN-VIVO/, Gene therapy, 3(10), 1996, pp. 932-936
Liver-directed gene therapy has the potential to provide an effective
adjutant to conventional treatments for liver diseases. In vivo gene t
ransfer is promising but still effectively out of reach with conventio
nal gene delivery techniques, Ex vivo gene therapy using hepatocyte tr
ansplantation, however, has been encouraging. We describe an approach
toward treatment of liver-related diseases by combining several of the
advantageous properties of current liver-directed therapies. Primary
hepatocytes were isolated, transduced with an adenovirus vector Encodi
ng a reporter gene, embedded in a collagen/polytetrafluoroethylene (PT
FE) lattice, and implanted in mice. Recovered 'hepatocyte-organoids' w
ere assayed for the presence and viability of the implanted hepatocyte
s, duration of transgene expression and presence of the adenovirus vec
tor. In an initial attempt, we demonstrate that genetically modified h
epatocytes can survive and express a transgene for at least 4 weeks in
vivo when embedded in a collagen/PTFE support and implanted in the in
traperitoneal cavity. This approach takes advantage of hepatocyte-spec
ific functions in order to treat diseases where a fraction of the norm
al enzymatic activity is sufficient to alleviate a disease phenotype.