title: Successful treatment of the murine model of cystinosis using bone marrow cell transplantation.
abstract: Cystinosis is an autosomal recessive metabolic disease that belongs to the family of lysosomal storage disorders. The defective gene is CTNS encoding the lysosomal cystine transporter, cystinosin. Cystine accumulates in every organ in the body and leads to organ damage and dysfunction, including renal defects. Using the murine model for cystinosis, Ctns(-/-) mice, we performed syngeneic bone marrow cell (BMC), hematopoietic stem cell (HSC), and mesenchymal stem cell transplantation. Organ-specific cystine content was reduced by 57% to 94% in all organs tested in the BMC-treated mice. Confocal microscopy and quantitative polymerase chain reaction revealed a large quantity of transplanted BMC in all organs tested, from 5% to 19% of the total cells. Most of these cells were not from the lymphoid lineage but part of the intrinsic structure of the organ. The natural progression of renal dysfunction was prevented, and deposition of corneal cystine crystals was significantly improved in the BMC-treated mice. HSC had the same therapeutic effect as whole BMC. In contrast, mesenchymal stem cell did not integrate efficiently in any organ. This work is a proof of concept for using HSC transplantation as a therapy for cystinosis and highlights the efficiency of this strategy for a chronic, progressive degenerative disease.
authors.affiliation: Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Syres
authors.forename: Frank
authors.initials: F
authors.lastname: Harrison
authors.forename: Matthew
authors.initials: M
authors.lastname: Tadlock
authors.forename: James V
authors.initials: JV
authors.lastname: Jester
authors.forename: Jennifer
authors.initials: J
authors.lastname: Simpson
authors.forename: Subhojit
authors.initials: S
authors.lastname: Roy
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Salomon
authors.forename: Stephanie
authors.initials: S
authors.lastname: Cherqui
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016026:Bone Marrow Transplantation; D003554:Cystinosis / Q000097:blood / Q000601:surgery* / Q000652:urine; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D018380:Hematopoietic Stem Cell Transplantation; D007124:Immunoenzyme Techniques; D008156:Luciferases / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution
chemical_list: D012333:RNA, Messenger; D008156:Luciferases