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Characterization of functionally distinct subpopulations of CD34+ cord
blood cells in serum-free long-term cultures supplemented with
hematopoietic cytokines
H Mayani, W Dragowska and PM Lansdorp
Division of Hematology, Terry Fox Laboratory, British Columbia Cancer
Agency, Vancouver, Canada.
We have previously identified, based on the expression of the CD45RA and
CD71 antigens, three major subpopulations of CD34+ cells derived from human
umbilical cord blood: CD34+ CD45RAloCD71lo cells (up to 42% multipotent
progenitors), CD34+ CD45RA+ CD71lo cells (90% myeloid progenitors), and
CD34+ CD45RAloCD71+ cells (70% erythroid progenitors). In the present
study, we have investigated the long-term proliferation and differentiation
of these subpopulations in response to hematopoietic cytokines. Cells from
each subpopulation were cultured for 38 days in serum- and stroma-free
liquid cultures supplemented with cytokine combinations that favor either
erythropoiesis or myelopoiesis. In keeping with their high content of
primitive progenitors, CD34+ CD45RAloCD71lo cells showed the highest CD34+
cell expansion (up to 532- fold) throughout the culture period, followed by
CD34+ CD45RA+ CD71lo (130-fold) and CD34+ CD45RAloCD71+ (28-fold) cells.
Interestingly, the cytokine combination favoring myelopoiesis was always
more efficient in inducing CD34+ cell expansion than the one favoring
erythropoiesis. In all but one of the cultures, a predominance of
myelopoiesis was observed after 2 weeks, even in those supplemented with
the cytokine mixture that favors erythropoiesis. Only when CD34+
CD45RAloCD71+ cells were cultured in the presence of erythroid cytokine
mixture, erythropoiesis was evident at all time points. However, such
cultures could be sustained for only 29 days. The results of this study
demonstrate that the cord blood-derived CD34+ cell compartment consists of
functionally distinct cell subpopulations that possess different
proliferative capacities in vitro. Our results also show that the cytokine
combinations used here were able to modulate proliferation and, to a much
lesser extent, differentiation of such subpopulations, probably by favoring
the expansion of committed progenitors rather than by acting on uncommitted
cells.
Volume 82,
Issue 9,
pp. 2664-2672,
11/01/1993
Copyright © 1993 by The American Society of Hematology
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