Hematopoietic progenitor cell mobilization into the peripheral blood of mice using a combination of recombinant rat stem cell factor (rrSCF) and recombinant human granulocyte colony-stimulating factor (rhG-CSF).
A significant increase in the hematopoietic stem cell (HSC) concentration has been observed in the peripheral blood and spleen of mice treated with rhG-CSF alone or with a combination of rhG-CSF plus rrSCF. The longer the duration of cytokine treatment, the higher the stimulatory effect on stem cell mobilization. In addition, cytokine administration led to a reduced stem cell concentration in the bone marrow. The total amount of HSCs in the body did not change following cytokine administration. These data support the theory that stem cells are mobilized from the bone marrow into circulation, as opposed to expanding in blood and spleen. In sharp contrast to rhG-CSF alone, a combination of rhG-CSF plus rrSCF produced a strong increase in the self-maintenance ability of peripheral blood day 11 colony-forming units-spleen (CFU-S-11). After 10 days of cytokine treatment, long-term culture initiating cells (LTC-IC) were seen in the peripheral blood; in normal mice, the content of LTC-IC in the blood was below the detection level. The activation of stromal progenitors (cells capable of transferring the hematopoietic microenvironment) by cytokine treatment was observed here for the first time. The results suggest that a combination of rhG-CSF plus rrSCF is more effective than rhG-CSF alone in obtaining a large amount of transplantable HSCs.
Drize
N
N
Hematological Scientific Center, Russian Academy of Medical Science, Moscow.
Chertkov
J
J
Zander
A
A
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000502:physiology*; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004347:Drug Interactions; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D019089:Stem Cell Factor / Q000494:pharmacology*; D013997:Time Factors
D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor