Reversion of hepatobiliary alterations by bone marrow transplantation in a murine model of erythropoietic protoporphyria

Fontanellas, Antonio; Mazurier, Frédéric; Landry, Marc; Taine, Laurence; Morel, Carine; Larou, Monique; Daniel, Jean-Yves; Montagutelli, Xavier; Salamanca, Rafael Enrı́quez de; Verneuil, Hubert de

doi:10.1053/jhep.2000.8531

Cited by 46 publications

(36 citation statements)

References 38 publications

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“…Bone marrow transplantation has the advantage of correcting the deficiency of ferrochelatase activity in the bone marrow. Experimental studies using bone marrow replacement in a mouse model of EPP, 34,35 as well as studies in a human with the disorder, 36 indicate that this will be the case. Patients receiving bone marrow transplantation for nonmalignant diseases generally have a 3-year survival rate of 70-90% if the donor is a matched sibling and 36-65% if the donor is unrelated.…”

Section: Discussionmentioning

confidence: 98%

Liver transplantation for erythropoietic protoporphyria liver disease

et al. 2005

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In erythropoietic protoporphyria (EPP), there is excessive production of protoporphyrin, primarily in the bone marrow, resulting in increased biliary excretion of this heme precursor. Some patients will develop progressive liver disease that may ultimately require liver transplantation. However, excessive production of protoporphyrin by the bone marrow continues after transplantation, which may cause recurrent disease in the allograft. This study was performed to define post-transplant survival, the risk of recurrent disease, and specific management issues in patients transplanted for EPP liver disease. The patients studied consisted of twelve males and eight females, with an average age of 31 (range, 13-56) years at the time of transplantation. The estimated maximum MELD score prior to transplant was 21 (range, 15-29). Unique complications in the perioperative period were light induced tissue damage in four patients and neuropathy in six, requiring prolonged mechanical ventilation in four. Patient and graft survival rates were 85% at 1 year, 69% at 5 years, and 47% at 10 years. Recurrent EPP liver disease occurred in 11 of 17 patients (65%) who survived more than 2 months. Three patients were retransplanted at 1.8, 12.6, and 14.5 years after the initial transplant for recurrent EPP liver disease. In conclusion, the 5-year patient survival rate in patients transplanted for EPP liver disease is good, but the recurrence of EPP liver disease appears to diminish long term graft and patient survival. (Liver Transpl 2005;11:1590-1596.)

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Section: Discussionmentioning

confidence: 98%

Liver transplantation for erythropoietic protoporphyria liver disease

et al. 2005

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“…It can also prevent hepatobiliary complications and reverse hepatic protoporphyrin accumulation. 19 BM cells and specifically hematopoietic stem cells (HSC) are considered as good targets for retrovirus-mediated gene therapy of immunological 21,22 and hematological 23 genetic diseases like EPP. One approach for gene therapy is to introduce ex vivo a normal counterpart of the defective gene into the HSC of the affected patient, and to return it as an autologous BM transplant.…”

Section: Discussionmentioning

confidence: 99%

“…Bone marrow cells were hybridized with a Y FITC labeled-paint probe for the mouse chromosome Y and a Cyanin 3 labeled-paint probe for the mouse chromosome X (Valbiotech, Paris, France), as described previously. 19 A minimum of 200 cells was examined.…”

Section: Analysis Of Chimerism In Transplanted Micementioning

confidence: 99%

“…An EPP patient who underwent allogeneic BM transplantation for leukemia had complete hematologic remission. 15 A murine model of EPP, the Fech m1Pas /Fech m1Pas mouse 16,17 was used for cell 18,19 and gene therapy. 18 The replacement of the major part of the deficient BM cells by normal ones was able to reduce protoporphyrin accumulation in erythrocytes.…”

Section: Introductionmentioning

confidence: 99%

“…18 Interestingly, BM transplantation performed in very young animals (3-4 weeks old) can prevent hepatobiliary complications as well as hepatocyte alterations and partially revert protoporphyrin accumulation in the liver. 19 However, allogeneic BM transplantation is limited by the need for an HLA-matched donor. In the absence of a suitable donor, autografting of genetically modified hematological cells seems to be an appealing alternative.…”

Section: Introductionmentioning

confidence: 99%

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