Cytokine-mediated expansion of 5-FU resistant peripheral blood stem cells and bone marrow: self-renewal and commitment capacity.

ABSTRACT

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)