Reversion of hepatobiliary alterations by bone marrow transplantation in a murine model of erythropoietic protoporphyria
Hepatology. 2000-07-01; 32(1): 73-81
DOI: 10.1053/jhep.2000.8531
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1. Hepatology. 2000 Jul;32(1):73-81.
Reversion of hepatobiliary alterations By bone marrow transplantation in a murine
model of erythropoietic protoporphyria.
Fontanellas A(1), Mazurier F, Landry M, Taine L, Morel C, Larou M, Daniel JY,
Montagutelli X, de Salamanca RE, de Verneuil H.
Author information:
(1)Laboratoire de Pathologie Mol¿eculaire et Th¿erapie G¿enique, Universit¿e
Victor Segalen Bordeaux 2, France.
Erythropoietic protoporphyria (EPP) is characterized clinically by cutaneous
photosensitivity and biochemically by the accumulation of excessive amounts of
protoporphyrin in erythrocytes, plasma, feces, and other tissues, such as the
liver. The condition is inherited as an autosomal dominant or recessive trait,
with a deficiency of ferrochelatase activity. A major concern in EPP patients is
the development of cholestasis with accumulation of protoporphyrin in
hepatobiliary structures and progressive cellular damage, which can rapidly lead
to fatal hepatic failure. The availability of a mouse model for the disease, the
Fech(m1Pas)/Fech(m1Pas) mutant mouse, allowed us to test a cellular therapy
protocol to correct the porphyric phenotype. When Fech/Fech mice received bone
marrow cells from normal animals, the accumulation of protoporphyrin in red blood
cells and plasma was reduced 10-fold but still remained 2.5 times above normal
levels. Interestingly, in very young animals, bone marrow transplantation can
prevent hepatobiliary complications as well as hepatocyte alterations and
partially reverse protoporphyrin accumulation in the liver. Bone marrow
transplantation may be an option for EPP patients who are at risk of developing
hepatic complications.
DOI: 10.1053/jhep.2000.8531
PMID: 10869291 [Indexed for MEDLINE]