title: Minimum requirement of donor cells to reduce the glycolipid storage following bone marrow transplantation in a murine model of Fabry disease.
abstract: BACKGROUND
  Fabry disease (FD) is a lysosomal storage disorders characterized by a deficiency of the lysosomal enzyme, α-galactosidase A. This results in the accumulation of glycolipids, mainly globotriaosylceramide (GL-3), in the lysosomes of various organs. Although bone marrow transplantation and hematopoietic stem cell-based gene therapy can offer the potential of a curative therapeutic outcome for FD, the minimum requirement of donor cells or gene-corrected cells to reduce GL-3 levels is not known.
  
  
  METHODS
  Lethally-irradiated FD mice were transplanted intravenously with normal bone marrow cells (Ly5.1 positive) mixed with those of FD mice (Ly5.2 positive) at various ratios to investigate the level of engraftment and enzyme activity necessary to effect a reduction in GL-3 storage.
  
  
  RESULTS
  Chimerism of whole white blood cells of recipients' peripheral blood remained stable at 8 weeks after transplantation, and chimerism of granulocytes, monocytes, B cells and T cells was equal to that of white blood cells. GL-3 levels were significantly reduced in the lung and heart of animals with a 30% and 50% chimera, respectively. The extent of reduction in these mice was almost identical to that with 100% chimera.
  
  
  CONCLUSIONS
  In FD mice, reconstitution with 100% donor cells is not required to obtain a therapeutic effect following bone marrow transplantation. These results suggest that a 30% gene correction might be sufficient to reverse disease manifestations in FD.
authors.affiliation: Department of Gene Therapy, Institute of DNA Medicine Higuchi, The Jikei University School of Medicine, Tokyo, Japan. t.yokoi@jikei.ac.jp
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yokoi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Yohta
authors.initials: Y
authors.lastname: Shimada
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Eto
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ishige
authors.forename: Teruo
authors.initials: T
authors.lastname: Kitagawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Otsu
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Nakauchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ida
authors.forename: Toya
authors.initials: T
authors.lastname: Ohashi
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D004195:Disease Models, Animal; D000795:Fabry Disease / Q000378:metabolism* / Q000628:therapy*; D006017:Glycolipids / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018183:Transplantation Chimera; D014281:Trihexosylceramides / Q000378:metabolism; D000519:alpha-Galactosidase / Q000378:metabolism
chemical_list: D006017:Glycolipids; D014281:Trihexosylceramides; C018549:globotriaosylceramide; D000519:alpha-Galactosidase