Long-term treatment of canine cyclic hematopoiesis with recombinant canine stem cell factor.
Grey collie dogs have cyclic fluctuations in their blood cell counts caused by a regulatory defect of hematopoietic stem cells. To examine the role of stem cell factor (SCF) or its receptor in this disorder, we investigated the stimulatory effects of recombinant canine SCF (rc-SCF) on in vitro marrow cultures, cloned and sequenced the grey collie SCF gene, and treated three grey collies with rc-SCF, either alone or in combination with recombinant canine granulocyte colony-stimulating factor (rcG-CSF). Colony-forming unit granulocyte-macrophage formation from grey collie or normal dog marrow showed similar dose-response curves for rc-SCF. Cloning and sequencing the SCF gene for two grey collies showed no evidence of mutations in the coding region of the SCF gene. Treatment with rc-SCF (10 to 100 micrograms/kg/d) did not induce neutrophilia except at the highest dose (100 micrograms/kg/d), but daily rc-SCF abrogated the neutropenic periods in doses of 20 micrograms/kg/d or greater. Combination of rc-G-CSF (0.5 to 1.0 microgram/kg/d) with rc-SCF treatment (20 to 50 micrograms/kg/d) suggested a synergistic effect, ie, the neutrophil levels on combined therapy were higher than the sum of the levels when these two cytokines were given separately. Long-term treatment of these dogs with rc-SCF in doses of 10 to 30 micrograms/kg/d was generally well tolerated, suggesting that SCF may be useful as a therapy for some chronic hypoproliferative disorders of hematopoiesis.
Dale
D C
DC
Department of Medicine, University of Washington School of Medicine, Seattle 98195.
Rodger
E
E
Cebon
J
J
Ramesh
N
N
Hammond
W P
WP
Zsebo
K M
KM
D000818:Animals; D001483:Base Sequence; D001853:Bone Marrow / Q000473:pathology; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use; D006098:Granulocytes / Q000166:cytology; D006402:Hematologic Diseases / Q000188:drug therapy / Q000662:veterinary*; D006410:Hematopoiesis; D016298:Hematopoietic Cell Growth Factors / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D008264:Macrophages / Q000166:cytology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009503:Neutropenia / Q000517:prevention & control; D011994:Recombinant Proteins / Q000627:therapeutic use; D019089:Stem Cell Factor
D016298:Hematopoietic Cell Growth Factors; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor