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 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.
Naffakh
N
N
Laboratoire Rétrovirus et Transfert Génétique, Centre National de la Recherche Scientifique 1157, Institut Pasteur, Paris.
Henri
A
A
Villeval
J L
JL
Rouyer-Fessard
P
P
Moullier
P
P
Blumenfeld
N
N
Danos
O
O
Vainchenker
W
W
Heard
J M
JM
Beuzard
Y
Y
D000818:Animals; D001483:Base Sequence; D017690:Cell Transplantation; D002478:Cells, Cultured; D004921:Erythropoietin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000637:transplantation*; D018014:Gene Transfer Techniques; D006400:Hematocrit; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000378:metabolism; D012867:Skin / Q000166:cytology*; D014161:Transduction, Genetic
D011994:Recombinant Proteins; D004921:Erythropoietin