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Blood, 15 November 2000, Vol. 96, No. 10, pp. 3399-3405
HEMATOPOIESIS
In vivo kinetics of murine hemopoietic stem cells
Janis L. Abkowitz,
Daniela Golinelli,
David E. Harrison, and
Peter Guttorp
From the Division of Hematology, Department of
Medicine, and the Department of Statistics, University of Washington,
Seattle, WA; and the Jackson Laboratory, Bar Harbor, ME.
We used stochastic modeling and computer simulation to study the
replication, apoptosis, and differentiation of murine hemopoietic stem
cells (HSCs) in vivo. This approach allows description of the behavior
of an unobserved population (ie, HSCs) on the basis of the behavior of
observed progeny cells (ie, granulocytes and lymphocytes). The results
of previous limiting-dilution, competitive-repopulation studies in 44 mice were compared with the results of simulated transplantation
studies to identify parameters that led to comparable outcomes. Using
this approach, we estimated that murine HSCs replicate (on average)
once every 2.5 weeks and that the frequency of murine HSCs is 8 per
105 nucleated marrow cells. If it is assumed that
short-term repopulating cells are distinct from HSCs, that they
contribute to hemopoiesis early after transplantation, and that they
are independently regulated, a frequency of 4 HSCs per 105
nucleated marrow cells also allows simulations that best approximate the observed data. When stochastic modeling and computer simulation were applied to limiting-dilution, autologous-transplantation studies in cats heterozygous for glucose-6-phosphate-dehydrogenase, different estimates of HSC replication rate (1 per 8.3-10 weeks) and
frequency (6 per 107 cells) were derived. Therefore, it
appears that these parameters vary inversely with increased longevity,
size, or both. An implication of these data is that human HSCs may be
less frequent and replicate more slowly. These findings on cell
kinetics have several implications.

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