Blood, 1 May 2003, Vol. 101, No. 9, pp. 3431-3435
HEMATOPOIESIS
Marrow frequency of rat long-term repopulating cells: evidence
that marrow hematopoietic stem cell concentration may be inversely
proportional to species body weight
Kenneth F. McCarthy
As measured by the long-term repopulating cell (LTRC) assay, only a
few hematopoietic stem cells (HSCs) or perhaps a single HSC are
required to totally repopulate the lymphohematopoietic tissues of
lethally irradiated mice, cats, and humans, raising the question as to
why large mammals require more marrow cells to either rescue them from
lethal irradiation or establish a long-term hematopoietic graft than do
small mammals. An explanation might be that HSC marrow frequency across
species is not constant, but decreases as species body weight
increases. This hypothesis was tested by comparing the LTRC marrow
concentration of mice to that of rats. Specifically, histocompatible
AKR/J Thy 1.1 marrow was transferred to 7-Gy irradiated C3H/HeN, Thy
1.2 mice, and histocompatible Norway Black marrow (NBr), RT 7.2 marrow
was transferred to 7-Gy irradiated RT 7.1 Lewis rats. The recipients
were scored for successful grafts 6 to 20 weeks later. By limiting
dilution analysis, a value of 1 LTRC/47 700 marrow cells was
calculated for mice, but only 1 LTRC/502 000 marrow cells was
calculated for rats. Viewed in the context of marrow grafting in larger
mammals, these results suggest that species with greater body mass have
lower marrow HSC frequency.