Correction of severe anaemia using immuno-regulated gene therapy is achieved by restoring the early erythroblast compartment.
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.
Du Roure
Camille
C
Lymphocyte Development Group, Medical Research Council, Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, London, UK. camille.duroure@fmi.ch
Takács
Katalin
K
Maxwell
Patrick H
PH
Roberts
Irene
I
Dazzi
Francesco
F
Cannella
Laura
L
Merkenschlager
Matthias
M
Fisher
Amanda G
AG
D019264:Adoptive Transfer / Q000379:methods*; D000740:Anemia / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D001853:Bone Marrow / Q000473:pathology; D003114:Colony-Forming Units Assay; D004900:Erythroblasts / Q000378:metabolism; D004920:Erythropoiesis; D004921:Erythropoietin / Q000235:genetics / Q000378:metabolism*; D015316:Genetic Therapy / Q000379:methods*; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D013154:Spleen / Q000473:pathology
D004921:Erythropoietin