The development of clinically applicable scaffolds is important for the application of
cell transplantation in various human diseases. The aims of this study are to evaluate
fibrin glue in a novel
protein replacement
therapy using proliferative adipocytes and to develop a mouse model system to monitor the delivery of the transgene product into the blood and the fate of the transduced cells after
transplantation. Proliferative adipocytes from mouse adipose tissue were transduced by a retroviral vector harboring the human
lecithin-cholesterol acyltransferase (lcat) gene, and were subcutaneously transplanted into mice combined with
fibrin glue. The lcat gene transduction efficiency and the subsequent secretion of the product in mouse adipocytes were enhanced using a
protamine concentration of 500 μg/ml. Adipogenesis induction did not significantly affect the lcat gene-transduced cell survival after
transplantation. Immunohistochemistry showed the ectopic
enzyme production to persist for 28 days in the subcutaneously transplanted gene- transduced adipocytes. The increased viability of transplanted cells with
fibrin glue was accompanied with the decrease in apoptotic cell death. The immunodetectable serum LCAT levels in mice implanted with the
fibrin glue were comparable with those observed in mice implanted with
Matrigel, indicating that the transplanted lcat gene-transduced adipocytes survived and functioned in the transplanted spaces with
fibrin glue as well as with
Matrigel for 28 days. Thus, this in vivo system using
fibrin is expected to serve as a good model to further improve the transplanted cell/scaffold conditions for the stable and durable cell-based replacement of defective
proteins in patients with
LCAT deficiency.