Effect of recombinant human stem cell factor on mafosfamide-treated bone marrow clonogenic cells.
The availability of early-acting cytokines could allow the establishment of new approaches to chemical marrow purging. It was the aim of the present study to investigate the capability of recombinant human stem cell factor (SCF) in combination with other growth factors to support the in vitro growth of mafosfamide-treated progenitor cells such as mixed colony forming units (CFU-GEMM), erythroid burst forming units (BFU-E) and granulocyte-macrophage CFU (CFU-GM). When marrow cells were incubated (30 min, 37 degrees C) with increasing doses of mafosfamide (30-120 micrograms/ml) a statistically significant (p < or = .05), dose-dependent suppression of colony growth was observed. Addition of SCF (50 ng/ml) to marrow cultures stimulated with the standard mixture of growth factors (interleukin 3 or IL-3, granulocyte-macrophage colony stimulating factor or GM-CSF, and erythropoietin or Epo) significantly increased the mean (+/- SD) concentration of mafosfamide inducing 95% inhibition of CFU-GM (106 +/- 17 versus 130 +/- 29, p < or = .0005), but not granulocyte/erythroid/macrophage/megakaryocyte CFU (CFU-GEMM) (85 +/- 4 versus 90 +/- 1, p < or = .1) and BFU-E (90 +/- 5 versus 92 +/- 5, p < or = .1). SCF induces a dose-dependent, statistically significant enhancement of colony formation by CD34+, mafosfamide-treated cells. As shown by single colony transfer experiments, mafosfamide-resistant clones promoted by SCF have a significantly higher replating capacity as compared with mafosfamide-resistant clones grown without SCF.(ABSTRACT TRUNCATED AT 250 WORDS)
Carlo-Stella
C
C
Department of Hematology, University of Parma, Italy.
Mangoni
L
L
Almici
C
C
Caramatti
C
C
Rizzoli
V
V
D015703:Antigens, CD; D018952:Antigens, CD34; D001853:Bone Marrow / Q000473:pathology; D016465:Bone Marrow Purging; D003114:Colony-Forming Units Assay; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D004357:Drug Synergism; D015672:Erythroid Precursor Cells / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014410:Tumor Stem Cell Assay
D015703:Antigens, CD; D018952:Antigens, CD34; D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; C048341:mafosfamide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide