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Publication : Sustained delivery of erythropoietin in mice by genetically modified skin fibroblasts.

First Author  Naffakh N Year  1995
Journal  Proc Natl Acad Sci U S A Volume  92
Issue  8 Pages  3194-8
PubMed ID  7724539 Mgi Jnum  J:25485
Mgi Id  MGI:73033 Doi  10.1073/pnas.92.8.3194
Citation  Naffakh N, et al. (1995) Sustained delivery of erythropoietin in mice by genetically modified skin fibroblasts. Proc Natl Acad Sci U S A 92(8):3194-8
abstractText  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 10(6)). 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.
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