title: Early stage transplantation of bone marrow cells markedly ameliorates copper metabolism and restores liver function in a mouse model of Wilson disease.
abstract: BACKGROUND
  Recent studies have demonstrated that normal bone marrow (BM) cells transplantation can correct liver injury in a mouse model of Wilson disease (WD). However, it still remains unknown when BM cells transplantation should be administered. The aim of this study was to investigate the potential impact of normal BM cells transplantation at different stages of WD to correct liver injury in toxic milk (tx) mice.
  
  
  METHODS
  Recipient tx mice were sublethally irradiated (5 Gy) prior to transplantation. The congenic wild-type (DL) BM cells labeled with CM-DiI were transplanted via caudal vein injection into tx mice at the early (2 months of age) or late stage (5 months of age) of WD. The same volume of saline or tx BM cells were injected as controls. The DL donor cell population, copper concentration, serum ceruloplasmin oxidase activity and aspartate aminotransferase (AST) levels in the various groups were evaluated at 1, 4, 8 and 12 weeks post-transplant, respectively.
  
  
  RESULTS
  The DL BM cells population was observed from 1 to 12 weeks and peaked by the 4th week in the recipient liver after transplantation. DL BM cells transplantation during the early stage significantly corrected copper accumulation, AST across the observed time points and serum ceruloplasmin oxidase activity through 8 to 12 weeks in tx mice compared with those treated with saline or tx BM cells (all P < 0.05). In contrast, BM cells transplantation during the late stage only corrected AST levels from 4 to 12 weeks post-transplant and copper accumulation at 12 weeks post-transplant (all P < 0.05). No significant difference was found between the saline and tx BM cells transplantation groups across the observed time points (P > 0.05).
  
  
  CONCLUSIONS
  Early stage transplantation of normal BM cells is better than late stage transplantation in correcting liver function and copper metabolism in a mouse model of WD.
authors.affiliation: Department of Rehabilitation Medicine, The First Affiliated Hospital, Sun Yat-Sen University, No 58 Zhongshan Road 2, Guangzhou 510080, PR China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Shihui
authors.initials: S
authors.lastname: Xing
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Feng
authors.forename: Songlin
authors.initials: S
authors.lastname: Chen
authors.forename: Zhong
authors.initials: Z
authors.lastname: Pei
authors.forename: Chuhuai
authors.initials: C
authors.lastname: Wang
authors.forename: Xiuling
authors.initials: X
authors.lastname: Liang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation; D003300:Copper / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006527:Hepatolenticular Degeneration / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D016133:Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D003300:Copper