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Alternative mechanisms with and without steel factor support primitive
human hematopoiesis
HJ Sutherland, DE Hogge, D Cook and CJ Eaves
Terry Fox Laboratory, BC Cancer Research Center, Vancouver, Canada.
As a first approach to defining the molecular requirements for supporting
human hematopoietic stem cell maintenance and differentiation in vitro, we
have analyzed and compared the ability of various factors to support the
maintenance and initial differentiation of human long-term
culture-initiating cells (LTC-ICs), a distinct, rare primitive
hematopoietic cell type whose progeny after 5 weeks include cells
detectable as colony-forming cells. Normal human marrow cells highly
enriched in LTC-ICs (approximately 1% pure) were placed in cultures
containing either preestablished, irradiated human marrow adherent feeder
layers, or feeders consisting of Steel factor-deficient SI/SI, or normal
+/+ murine fibroblasts, or no feeders. In some groups, either Steel factor
alone, granulocyte colony-stimulating factor (G- CSF) and interleukin-3
(IL-3), or all three factors combined were also added repeatedly. SI/SI
murine fibroblasts were equivalent to +/+ controls and to normal human
marrow feeders in supporting both LTC-IC maintenance and clonogenic cell
output over a 5-week period. Soluble Steel factor alone could, however,
effectively substitute for human marrow feeders to support LTC-IC
maintenance, although clonogenic cell output was markedly reduced under
these conditions. Conversely, soluble Steel factor with G-CSF and IL-3 or
with feeders (or all together) did not further enhance (or depress) LTC-IC
maintenance, although under these conditions clonogenic cell output was
markedly increased. These findings confirm previous evidence that LTC-IC
maintenance and clonogenic cell production are differentially regulated and
show for the first time that LTC-IC maintenance can be supported by
different nonsynergizing factors that may, but need not, include Steel
factor.
Volume 81,
Issue 6,
pp. 1465-1470,
03/15/1993
Copyright © 1993 by The American Society of Hematology
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