title: Bone marrow-derived cells promote liver regeneration in mice with erythropoietic protoporphyria.
abstract: BACKGROUND
  Bone marrow transplantation can reverse hepatic protoporphyrin accumulation and prevent the hepatobiliary complications characteristic of erythropoietic protoporphyria. The aim of this study was to assess the recruitment capacity of bone marrow cells in the damaged liver and their possible contribution to the improved or recovered hepatic function in a murine model of erythropoietic protoporphyria (EPP).
  
  
  METHODS
  Lethally irradiated female EPP mice were transplanted with bone marrow cells from healthy male mice and were monitored during 12 or 36 weeks. Two groups of animals killed 12 weeks after transplant were also treated with granulocyte colony-stimulating factor.
  
  
  RESULTS
  Cell transplantation decreased porphyrin contents in erythrocytes and liver. Improved hepatic structure and function and reduced hepatic fibrosis were observed, especially 36 weeks after transplant. Bone marrow-derived cells (22%-35%) were identified in the liver of recipient mice by means of fluorescence in situ hybridization (chrY-FISH) or green fluorescent protein staining and were characterized by immunofluorescence staining. The livers of recipients contained 20% to 30% myofibroblasts (alpha-smooth muscle actin-positive cells), 40% CK19-positive cells, and 10% to 28% hepatocytes (albumin-positive cells) derived from the donor bone marrow.
  
  
  CONCLUSIONS
  Bone marrow-derived cells play a significant role in restoring and regenerating hepatic tissue in EPP mice. Hepatic repair was associated with fibrogenesis, enhanced by granulocyte colony-stimulating factor treatment, and almost normal liver structure and function was observed in the long term (36 weeks posttransplant).
authors.affiliation: Research Centre 12 de Octubre University Hospital, Madrid, Spain. maria.garciabravo@ciemat.es
authors.forename: María
authors.initials: M
authors.lastname: García-Bravo
authors.forename: María-Josefa
authors.initials: MJ
authors.lastname: Morán-Jiménez
authors.forename: Oscar
authors.initials: O
authors.lastname: Quintana-Bustamante
authors.forename: Manuel
authors.initials: M
authors.lastname: Méndez
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Gutiérrez-Vera
authors.forename: Juan
authors.initials: J
authors.lastname: Bueren
authors.forename: Eduardo
authors.initials: E
authors.lastname: Salido
authors.forename: José-Carlos
authors.initials: JC
authors.lastname: Segovia
authors.forename: Antonio
authors.initials: A
authors.lastname: Fontanellas
authors.forename: Rafael Enríquez
authors.initials: RE
authors.lastname: de Salamanca
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D017404:In Situ Hybridization, Fluorescence; D008099:Liver / Q000473:pathology*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D046351:Protoporphyria, Erythropoietic / Q000188:drug therapy / Q000473:pathology / Q000601:surgery*; D011994:Recombinant Proteins; D016896:Treatment Outcome
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor