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Título : Bone marrow-derived cells promote liver regeneration in mice with erythropoietic protoporphyria
Autor : García-Bravo, María
Morán-Jiménez, María José
Quintana-Bustamante, Óscar
Méndez, Manuel
Gutiérrez-Vera, Inmaculada
Bueren, Juan
Salido, Eduardo
Segovia, José Carlos
Fontanellas, Antonio
Enríquez de Salamanca, Rafael
Palabras clave : erythropoietic protoporphyria
bone marrow-derived hepatocytes
cell therapy
liver regeneration
liver repair
Fecha de publicación : 27-dic-2009
Editorial : Transplantation
Citación : García-Bravo M, Morán-Jiménez MJ, Quintana-Bustamante O, Méndez M, Gutiérrez-Vera I, Bueren J, Salido E, Segovia JC, Fontanellas A, de Salamanca RE. Bone marrow-derived cells promote liver regeneration in mice with erythropoietic protoporphyria. Transplantation. 2009 Dec 27;88(12):1332-40. doi: 10.1097/TP.0b013e3181bce00e. PMID: 20029329.
Resumen : 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).
URI : http://documenta.ciemat.es/handle/123456789/2583
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