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Correction of severe anaemia using immuno‐regulated gene therapy is achieved by restoring the early erythroblast compartment
Author(s) -
Du Roure Camille,
Takács Katalin,
Maxwell Patrick H.,
Roberts Irene,
Dazzi Francesco,
Cannella Laura,
Merkenschlager Matthias,
Fisher Amanda G.
Publication year - 2006
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2005.05905.x
Subject(s) - erythroblast , erythropoietin , erythropoiesis , bone marrow , population , spleen , immunology , medicine , biology , anemia , environmental health
Summary Patients with chronic renal failure usually require exogenous erythropoietin (epo) to alleviate anaemia resulting from inadequate epo production by the kidneys. We have recently shown that severe anaemia in genetically manipulated epo‐deficient mice (EpoTAg) can be corrected by adoptively transferred epo‐producing lymphocytes. The aim of this study was to investigate the precise effects of human epo administration by this route on erythropoietic development in epo‐deficient mice. The erythroblast compartments of untreated and treated EpoTAg mice were analysed in comparison with wild‐type mice. The early erythroblast population was reduced in the bone marrow of epo‐deficient mice, whilst the number of erythroid colony‐forming units (CFU‐E) was not significantly compromised. This paucity in marrow early erythroblasts was restored to normal values in treated mutant mice. In addition, the early erythroblast population was expanded in the spleens of treated animals. These findings show that the early erythroblasts are important targets of epo and that epo corrects anaemia of epo‐deficient mice by restoring marrow function and splenic erythropoiesis.