Phenotypic and immunologic characteristics of docetaxel-mobilized peripheral blood stem cells in mice.
Effective mobilization of peripheral blood stem cells is vital for transplantation of patients after high-dose chemotherapy and provides a convenient source of stem cells for genetic engineering and other studies, but optimal mobilization strategies have not been defined. Recent studies show that in the presence of recombinant human granulocyte colony-stimulating factor (rhG-CSF), docetaxel (DXT) is an effective mobilization agent. This study was performed to evaluate the phenotype and immunologic properties of DXT-mobilized stem cells. Administration of DXT + rhG-CSF to normal C57Bl/6 mice induced a 75-fold increase in blood hematopoietic progenitors and a significant increase in both CD3(+) (T cell) and DX5(+) [natural killer (NK)] cells when compared to untreated mice. The cytotoxicity of DXT + rhG-CSF-mobilized cell populations against YAC-1 and B16F10 cell lines was not significantly different from that of untreated mice. When compared to cyclophosphamide + rhG-CSF, DXT + rhG-CSF-mobilized cell populations yielded a greater number of T and NK cells, with significantly higher cytotoxic effector function. These results suggest that DXT + rhG-CSF-mobilized PBSCs retain potent immunologic capacity with a high number of the functional cellular subsets than those normally present in peripheral blood, which may be important in maintaining the antitumor immunity after transplantation.
Ojeifo
John O
JO
Department of Oncology, Georgetown University Medical Center, Washington, DC 20007, USA. ojeifoj@georgetown.edu
Wu
Aiguo G
AG
Herscowitz
Herbert B
HB
Meehan
Kenneth R
KR
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D000077143:Docetaxel; D004359:Drug Therapy, Combination; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D007694:Killer Cells, Natural; D007958:Leukocyte Count; D016131:Lymphocyte Subsets; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011994:Recombinant Proteins; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology*
D015703:Antigens, CD; D017252:CD3 Complex; D011994:Recombinant Proteins; D043823:Taxoids; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; D003520:Cyclophosphamide