Engraftment of genetically engineered amniotic epithelial cells corrects lysosomal storage in multiple areas of the brain in mucopolysaccharidosis type VII mice

Cell-mediated gene therapy for visceral lesions of lysosomal storage diseas es is promising; however, the treatment of central nervous system (CNS) les ions remains a challenge. In this study, we generated rat amniotic epitheli al cells (AEC) that overexpress and secrete human beta -glucuronidase (GUSB ) following transduction with an adenoviral vector encoding human GUSB. The AEC were used as donor cells for cell-mediated gene therapy of CNS lesions in mice with mucopolysaccharidosis type VII (MPSVII), a lysosomal storage disorder caused by an inherited deficiency of GUSB activity. After confirma tion that the secreted GUSB was taken up mainly via mannose 6-phosphate rec eptors in primary cultured neurons, the AEC were transplanted into the brai ns of adult MPSVII mice. Histochemical analysis showed extensive GUSB activ ity throughout the ipsilateral hemisphere of the recipient brains, and path ological improvement of the lysosomal storage was observed even in regions far from the site of injection. These results suggest that intracerebral tr ansplantation of genetically engineered AEC has therapeutic potential for t he treatment of CNS lesions in lysosomal storage disorders.