Widespread distribution of adenovirus-transduced monkey amniotic epithelial cells after local intracerebral injection: Implication for cell-mediated therapy for lysosome storage disorders

Cell-mediated therapy for mucopolysaccharidosis type VII (MPSVII) was studi ed using monkey amniotic epithelial cells (mAEC). The cells were transduced with a recombinant adenovirus expressing human beta -glucuronidase (GUSB), and cells overexpressing GUSB were generated. The cells expressed 2000-fol d higher activities than the endogenous GUSB activities of nontransduced mA EC, demonstrating that mAEC were successfully transduced with adenoviral ve ctors. These cells also secreted high levels of GUSB. To clarify the cross- correction of GUSB secreted from mAEC, the conditioned medium containing hi gh levels of GUSB was added into the medium for culturing human or murine f ibroblasts established from an MPSVII patient or a mouse model of the disea se. Dramatic increases in GUSB activities were observed in both fibroblasts . We then transplanted the cells transduced with an adenovirus expressing L acZ into the caudate-putamen of monkey brain. Survival and distribution of the transplanted cells 1 month after the treatment were evaluated, Histoche mical analysis showed that LacZ-positive cells were widely distributed in t he brain, suggesting that the transplanted cells had migrated and were dist ributed even at regions far from the implantation site. These findings sugg est that local intracerebral engraftment of genetically engineered amniotic epithelial cells is favorable for the treatment of lysosome storage disord ers, whose pathological abnormalities are not restricted to specific region s of the brain.