title: Reduction of lysosomal storage in murine mucopolysaccharidosis type VII by transplantation of normal and genetically modified macrophages.
abstract: This study examined the ability of macrophages to serve as target cells of gene therapy for mucopolysaccharidosis (MPS) type VII using a murine model. Bone marrow cells were harvested from syngeneic normal mice and differentiated to macrophages. These cells were given to nonmyeloablated MPS VII mice. After transplantation, donor cells populated the liver and spleen. The pathologic improvement at day 38 after transplantation was significant and glycosaminoglycan storage was reduced. To develop gene therapy using this system, a retroviral vector expressing human beta-glucuronidase (HBG) was used to infect macrophages cultivated from MPS VII mice and given to nonmyeloablated MPS VII mice. At 38 days after transplantation, HBG-positive cells were still observed histochemically and pathologic improvement was significant. These observations suggest that macrophage transplantation is a promising method for treatment of murine MPS VII without myeloablation, and macrophages may be good target cells for ex vivo gene therapy for MPS VII.
authors.affiliation: Department of Gene Therapy, Institute of DNA Medicine, Jikei University School of Medicine, Tokyo, Japan. tohashi@gd5.so-net.ne.jp
authors.forename: T
authors.initials: T
authors.lastname: Ohashi
authors.forename: T
authors.initials: T
authors.lastname: Yokoo
authors.forename: S
authors.initials: S
authors.lastname: Iizuka
authors.forename: H
authors.initials: H
authors.lastname: Kobayashi
authors.forename: W S
authors.initials: WS
authors.lastname: Sly
authors.forename: Y
authors.initials: Y
authors.lastname: Eto
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D004195:Disease Models, Animal; D015316:Genetic Therapy; D005966:Glucuronidase / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D007728:Kupffer Cells / Q000473:pathology / Q000648:ultrastructure; D008247:Lysosomes / Q000473:pathology / Q000648:ultrastructure*; D008264:Macrophages / Q000166:cytology / Q000637:transplantation*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D016538:Mucopolysaccharidosis VII / Q000628:therapy*; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection; D014185:Transplantation, Isogeneic
chemical_list: D011994:Recombinant Proteins; D005966:Glucuronidase