Cytokine-mediated expansion of 5-FU resistant peripheral blood stem cells and bone marrow: self-renewal and commitment capacity.
To further characterize the primitive stem cell subpopulation present in chemotherapy mobilized peripheral blood stem cells (PBSC), we evaluated the functional characteristics of 5-FU-resistant PBSC and normal bone marrow (BM) cells after 7 days incubation with IL-1 + IL-3+SCF. The resulting 5-FU-resistant cells were evaluated for (1) the production of GM-CSF-responsive clonogenic elements (CE), (2) the production of IL-3+GM-CSF-responsive CE, and (3) their self-renewal capacity (production of IL-1+IL-3+SCF-responsive CE). We also evaluated the percentage of CD34+ cells, the percentage of cells in S phase of the cell cycle, and the number of nucleated cells before and after cytokine-mediated expansion. We demonstrated an overall loss in nucleated cells after cytokine-mediated expansion in all cell fractions. We demonstrated a significantly greater increase in the percentage of CD34+ cells in the 5-FU-resistant PBSC fraction as compared to 5-FU-resistant BM cells (p = 0.012). We also showed that 5-FU-resistant PBSC have a greater capacity for self-renewal, amplification of IL-3+GM-CSF-responsive progenitors, and the production of committed GM-CSF-responsive progenitors as compared with BM cells, but this did not reach statistical significant. These results suggest that PBSC contain a truly primitive stem cell with an enhanced self-renewal and differentiative capacity that is recruited by 5-FU resistance and IL-1+IL-3+CSF-mediated expansion.(ABSTRACT TRUNCATED AT 250 WORDS)
Rice
A
A
Laboratoire de Greffe de Moelle, URA CNRS 1456, Université de Bordeaux II, France.
Boiron
J M
JM
Barbot
C
C
Dupouy
M
M
Dubsoc-Marchenay
N
N
Dumain
P
P
Lacombe
F
F
Reiffers
J
J
D015703:Antigens, CD / Q000097:blood; D018952:Antigens, CD34; D001853:Bone Marrow / Q000187:drug effects*; D002467:Cell Nucleus / Q000502:physiology; D016207:Cytokines / Q000494:pharmacology*; D004351:Drug Resistance / Q000502:physiology; D005472:Fluorouracil / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D016196:S Phase
D015703:Antigens, CD; D018952:Antigens, CD34; D016207:Cytokines; D005472:Fluorouracil