Systemic production of human granulocyte colony-stimulating factor in nonhuman primates by transplantation of genetically modified myoblasts

Citation
Pa. Moisset et al., Systemic production of human granulocyte colony-stimulating factor in nonhuman primates by transplantation of genetically modified myoblasts, HUM GENE TH, 11(9), 2000, pp. 1277-1288
Citations number
44
Categorie Soggetti
Molecular Biology & Genetics
Journal title
HUMAN GENE THERAPY
ISSN journal
10430342 → ACNP
Volume
11
Issue
9
Year of publication
2000
Pages
1277 - 1288
Database
ISI
SICI code
1043-0342(200006)11:9<1277:SPOHGC>2.0.ZU;2-G
Abstract
Clinical use of human granulocyte-colony stimulating factor (hG-CSF) to tre at various diseases involving neutropenia has been previously shown to (1) successfully increase circulating neutrophils, (2) reduce condition-related infections, and (3) cause few side effects in patients. To alleviate the s ymptoms of neutropenia, the patient must receive frequent injections of rec ombinant hG-CSF. Permanent ways to deliver stable levels of the molecule to the patient are being investigated. Among them, the transplantation of hG- CSF-secreting cells has been proposed and performed successfully in rodents , using fibroblast cell lines and primary muscle cells. We thus investigate d whether similar results could be obtained by intramuscular myoblast trans plantation in a large animal model. When 1-3 X 10(8) myoblasts were injecte d into three Macaca mulatta, hG-CSF was detected at high levels (300-900 pg /ml), which in turn led to a four-to fivefold increase in circulating neutr ophils. However, both the concentrations of hG-CSF and neutrophil levels we re found to decrease over time. Nonetheless, neutrophils were found at high er levels from the fourth week until the end the experiment (up to 29 weeks ) in G-CSF monkeys compared with control animals. These results show that t ransplantation of hG-CSF-secreting myoblasts may indeed be a therapeutic op tion for the treatment of neutropenic patients.