Cytokine-mediated expansion of 5-FU-resistant peripheral blood stem cells.
We evaluated the expansion capacity of untreated and 5-fluorouracil (5-FU)-resistant peripheral blood stem cells (PBSC) after 7-day incubation with interleukin-1 (IL-1) plus IL-3 plus stem cell factor (SCF) or with medium alone. We found a significant increase in the proportion of CD34+ cells in the PBSC fraction resistant to 25 micrograms/mL 5-FU after 7-day incubation with IL-1 plus IL-3 plus SCF as compared with the untreated fraction (p = 0.011). We also showed that 5-FU-resistant PBSC have a greater capacity for expansion of IL-1/IL-3/SCF-responsive immature progenitors (p = 0.05), amplification of IL-3 plus GM-CSF responsive progenitors (p = 0.01), and production of committed single growth factor-responsive (granulocyte-macrophage colony-stimulating factor [GM-CSF]) precursors (p = 0.01) than the untreated PBSC. The expansion of all types of progenitors and CD34+ cells was only observed after 7-day incubation with IL-1 plus IL-3 plus SCF. These results suggest that PBSC contain a primitive stem cell population with an enhanced expansion capacity that is identified by 5-FU resistance. As these cells can be expanded in vitro, they may then be suitable for a number of clinical applications.
Rice
A
A
Laboratoire de Greffe de Moelle, Université de Bordeaux II, France.
Boiron
J M
JM
Barbot
C
C
Dupouy
M
M
Dubosc-Marchenay
N
N
Dumain
P
P
Lacombe
F
F
Reiffers
J
J
D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34; D001773:Blood Cells / Q000187:drug effects; D002453:Cell Cycle; D002469:Cell Separation / Q000379:methods; D016238:Cytapheresis; D004351:Drug Resistance; D005472:Fluorouracil / Q000494:pharmacology*; D016298:Hematopoietic Cell Growth Factors / Q000008:administration & dosage*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000008:administration & dosage*; D007377:Interleukin-3 / Q000008:administration & dosage*; D019089:Stem Cell Factor
D015703:Antigens, CD; D018952:Antigens, CD34; D016298:Hematopoietic Cell Growth Factors; D007375:Interleukin-1; D007377:Interleukin-3; D019089:Stem Cell Factor; D005472:Fluorouracil