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Extended long-term culture reveals a highly quiescent and primitive human
hematopoietic progenitor population
QL Hao, FT Thiemann, D Petersen, EM Smogorzewska and GM Crooks
Division of Research Immunology and Bone Marrow Transplantation, Childrens
Hospital Los Angeles, CA 90027, USA.
Long-term culture-initiating cells (LTC-IC) are hematopoietic progenitors
able to generate colony-forming unit-cells (CFU) after 5 to 8 weeks (35 to
60 days) of culture on bone marrow (BM) stroma and represent the most
primitive progenitors currently detectable in vitro. We have recently
reported that long-term cultures initiated with CD34+CD38- cells from BM or
cord blood are able to continue generating CFU for at least 100 days, ie,
beyond the standard LTC-IC period. In this report, single-cell cultures
from cord blood and retroviral marking of cord blood and BM were used to
study whether the subpopulation of CD34+CD38- cells able to generate CFU
beyond 60 days ("extended long-term culture-initiating cells" or ELTC-IC)
are functionally distinct from LTC-IC in terms of timing of initial clonal
proliferation and generative capacity. All cord blood LTC-IC formed clones
of greater than 50 cells by day 30. In contrast, cord blood ELTC- IC
proliferated later in culture, 50% forming clones after day 30. Although
efficient retroviral marking of LTC-IC was seen (25% to 45%), marking of
ELTC-IC was inefficient (< 1%), consistent with a more quiescent
progenitor population. There was a positive correlation between time of
clonal proliferation and generative capacity. ELTC-IC generated threefold
to fourfold more progeny than did LTC-IC (P < .002). These studies show
that there is a functional hierarchy of progenitors in long-term culture
which correlates with their level of quiescence. By extending the LTC-IC
assay, a more primitive progenitor may be studied that may be functionally
closer to the human long-term repopulation stem cell in vivo.
Volume 88,
Issue 9,
pp. 3306-3313,
11/01/1996
Copyright © 1996 by The American Society of Hematology
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