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Blood, 15 May 2001, Vol. 97, No. 10, pp. 3061-3068
HEMATOPOIESIS
The relative quiescence of hematopoietic stem cells in nonhuman
primates
Nadim Mahmud,
Steven M. Devine,
Kevin P. Weller,
Simrit Parmar,
Cord Sturgeon,
Mary C. Nelson,
Terry Hewett, and
Ronald Hoffman
From the Hematology/Oncology Section and
Transplantation Surgery Section, Biologic Resources Laboratory,
University of Illinois College of Medicine, Chicago.
Quiescence has been thought to be required for the retention of the
full biological potential of pluripotent hematopoietic stem cells
(PHSCs). This hypothesis has been challenged recently by the
observation that all murine PHSCs cycle continuously and constantly
contribute to steady-state blood cell production. It was asked
whether these observations could be extrapolated to describe
hematopoiesis in higher mammals. In this series of experiments, the
replicative history of PHSCs was examined in baboons by continuously administering bromodeoxyuridine (BrdU) for more than 85 weeks. The
results indicate that under steady-state conditions, PHSCs remain
largely quiescent but do cycle, albeit at a far lower rate than
previously reported for rodent PHSCs. BrdU-labeled cycling PHSCs and
progenitor cells were shown to have an extensive proliferative capacity
and to contribute to blood cell production for prolonged periods
of time. The proportion of PHSCs entering cell cycle could, however, be
rapidly increased by the in vivo administration of granulocyte-colony
stimulating factor. These data indicate that during
steady-state hematopoiesis, baboon PHSCs require prolonged periods of
time to cycle and that the proportion of PHSCs in cycle is not fixed
but can be altered by external stimuli. The relative quiescence of
PHSCs observed in this nonhuman primate model, in contrast to murine
PHSCs, might explain the current barriers to genetic modification and
ex vivo expansion of human PHSCs.
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