Bone marrow transplantation into hemochromatotic mice decreases hepatic and duodenal iron overload.
Human hereditary hemochromatosis is a disorder of iron homeostasis characterized by increased absorption of iron and its deposition in parenchymal organs. The maintenance of iron homeostasis is regulated by molecules involved in the absorption, transport, storage and redox of iron. The potential of hematopoietic stem cell therapy for liver diseases has been studied in some experimental animal models. Our objective was to evaluate the effect of bone marrow transplantation from wild type mice on the status of iron overload in Hfe knockout hemochromatotic mice (Hfe(-/-)). The transplanted cells were detected in the liver (11% of the total cells) and characterized as hepatocytes and myofibroblasts. They were also detected in the duodenum and characterized as myofibroblasts. The iron content in the Hfe(-/-) mice descended 2.9-fold in the liver and 2.4-fold in the duodenum 6 months after transplantation. Non-significant changes of relative mRNA abundance of genes of iron metabolism were observed in the liver and duodenum of Hfe(-/-) transplanted mice. At 6 months after transplantation the proportion of Hfe mRNA in Hfe(-/-) mice reached 3.8% of the levels in wild type mice in the liver and 1.6% in the duodenum. In conclusion, adult stem cells from bone marrow transplant were able to differentiate into hepatocytes and myofibroblasts in hemochromatotic mice. Bone marrow transplantation assisted in reducing the iron overload in this murine model of hemochromatosis. These findings might contribute to the knowledge of pathways involved in the regulatory system of iron homeostasis.
Morán-Jiménez
María-Josefa
MJ
Research Centre, 12 de Octubre University Hospital, Madrid, 28041, Spain. moranjimenez@h12o.es
García-Bravo
María
M
Méndez
Manuel
M
Gutiérrez-Vera
Inmaculada
I
Grau
Montserrat
M
Navarro-Ordoñez
Susana
S
Fontanellas
Antonio
A
Enríquez-de-Salamanca
Rafael
R
D000818:Animals; D016026:Bone Marrow Transplantation; D004386:Duodenum / Q000378:metabolism; D005260:Female; D006432:Hemochromatosis / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D019190:Iron Overload / Q000378:metabolism* / Q000628:therapy*; D035925:Iron-Regulatory Proteins / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal
D000071020:Hemochromatosis Protein; C499535:Hfe protein, mouse; D015395:Histocompatibility Antigens Class I; D035925:Iron-Regulatory Proteins; D008565:Membrane Proteins