Abstract | BACKGROUND & AIMS: METHODS: We studied the development of liver disease from birth in EPP mice, in relation with erythroid and hepatic PPIX accumulation. To prevent the development of liver disease, BMT was performed into newborn mice using a novel busulfan-mediated preconditioning assay. RESULTS: We showed that hepatic PPIX accumulates during the first 2 weeks and correlates with the onset of a progressive liver fibrosis in 12-day-old EPP mice. Transplantation of normal congenic hematopoietic stem cells into EPP neonates led to long-term donor hematopoiesis recovery. A full correction of erythroid PPIX accumulation and skin photosensitivity was obtained. Furthermore, five months after neonatal BMT, liver damage was almost completely prevented. CONCLUSIONS: We demonstrated for the first time that BMT could be successfully used to prevent liver disease in EPP mice and suggested that BMT would be an attractive therapeutic option to prevent severe liver dysfunction in EPP patients.
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Authors | Yann Duchartre, Nicolas Petit, Corrine Moya, Magalie Lalanne, Pierre Dubus, Hubert de Verneuil, François Moreau-Gaudry, Emmanuel Richard |
Journal | Journal of hepatology
(J Hepatol)
Vol. 55
Issue 1
Pg. 162-70
(Jul 2011)
ISSN: 1600-0641 [Electronic] Netherlands |
PMID | 21145811
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. |
Chemical References |
- Myeloablative Agonists
- Protoporphyrins
- protoporphyrin IX
- Ferrochelatase
- Busulfan
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Topics |
- Animals
- Animals, Newborn
- Bone Marrow Transplantation
- Busulfan
(administration & dosage)
- Disease Models, Animal
- Disease Progression
- Ferrochelatase
(genetics)
- Humans
- Liver
(metabolism, pathology)
- Liver Diseases
(etiology, metabolism, pathology, prevention & control)
- Liver Failure
(prevention & control)
- Mice
- Mice, Congenic
- Mice, Inbred C57BL
- Mice, Mutant Strains
- Myeloablative Agonists
(administration & dosage)
- Protoporphyria, Erythropoietic
(complications, enzymology, genetics, therapy)
- Protoporphyrins
(metabolism)
- Transplantation Conditioning
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