Sustained Delivery of Erythropoietin in Mice by Genetically Modified Skin Fibroblasts

We have examined whether the secretion of erythropoietin (Epo) from genetically modified cells could represent an alternative to repeated injections of the recombinant hormone for treating chronic anemias responsive to Epo. Primary mouse skin fibroblasts were transduced with a retroviral vector in w...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1995-04, Vol.92 (8), p.3194-3198
Main Authors: Naffakh, N., Henri, A., Villeval, J. L., Rouyer-Fessard, P., Moullier, P., Blumenfeld, N., Danos, O., Vainchenker, W., Heard, J. M., Beuzard, Y.
Format: Article
Language:English
Subjects:
3T3 cells
Animals
Base Sequence
Cell culture techniques
Cell lines
Cell Transplantation
Cells
Cells, Cultured
Complementary DNA
Epics
Erythropoietin - blood
Erythropoietin - genetics
Erythropoietin - metabolism
Fibroblasts
Fibroblasts - transplantation
Gene Transfer Techniques
Genetically modified organisms
Hematocrit
Mice
Mice, Inbred DBA
Molecular Sequence Data
Recombinant Proteins - metabolism
Skin - cytology
Transduction, Genetic
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Summary:We have examined whether the secretion of erythropoietin (Epo) from genetically modified cells could represent an alternative to repeated injections of the recombinant hormone for treating chronic anemias responsive to Epo. Primary mouse skin fibroblasts were transduced with a retroviral vector in which the murine Epo cDNA is expressed under the control of the murine phosphoglycerate kinase promoter. "Neo-organs" containing the genetically modified fibroblasts embedded into collagen lattices were implanted into the peritoneal cavity of mice. Increased hematocrit (>80%) and elevated serum Epo concentration (ranging from 60 to 408 milliunits/ml) were observed in recipient animals over a 10-month observation period. Hematocrit values measured in recipient mice varied according to the number of implanted Epo-secreting fibroblasts (ranging from 2.5 to 20 x 106). The implantation of neo-organs containing Epo-secreting fibroblasts appeared, therefore, as a convenient method to achieve permanent in vivo delivery of the hormone. We estimated that the biological efficacy of the approach may be relevant for the treatment of human hemoglobinopathies.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.92.8.3194