SUSTAINED DELIVERY OF ERYTHROPOIETIN IN MICE BY GENETICALLY-MODIFIED SKIN FIBROBLASTS

We have examined whether the secretion of erythropoietin (Epo) from ge netically modified cells could represent an alternative to repeated in jections of the recombinant hormone for treating chronic anemias respo nsive to Epo. Primary mouse skin fibroblasts were transduced with a re troviral vector in which the murine Epo cDNA is expressed under the co ntrol of the murine phosphoglycerate kinase promoter. ''Neo-organs'' c ontaining 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 6 0 to 408 milliunits/ml) were observed in recipient animals over a 10-m onth 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 conta ining Epo-secreting fibroblasts appeared, therefore, as a convenient m ethod to achieve permanent in vivo delivery of the hormone. We estimat ed that the biological efficacy of the approach may be relevant for th e treatment of human hemoglobinopathies.