Hematopoietic Stem Cell Regulation. II. Chronic Effects of Hypoxic-Hypoxia on CFU Kinetics

Hypobaric-hypoxia, an established stimulator of erythropoiesis, was used to perturb normal steady-state hematopoiesis and thereby to facilitate an analysis of stem cell kinetics. BDF₁ male mice were exposed to a simulated altitude of 22,000 ft for 1-15 days. The following parameters were assessed at daily intervals: packed red cell volumes (PCV), femoral and splenic nucleated cellularity, the relative concentration and total number of colony-forming units (CFU, i.e., stem cells) in the femoral shaft and whole spleen, as well as the turnover of this population of cells using the "³H-thymidine-killing" technique. By 10 days of hypoxia the PCV had risen to 65% and by a fortnight was elevated to, and stabilized at, 70%-75%. After an evanescent increase, the femoral cellularity became slightly hypocellular but returned to normal by 3 days, thence becoming hypercellular from days 5 to 15. The spleen was markedly depleted of cells for 48 hr and recovered to hypercellular levels between 4 and 6 days. It then oscillated from hypercellular to normal levels with a period interval of 5 days. Both femoral and splenic CFU demonstrated oscillations, as did the estimations made on the state of CFU turnover. The femoral and splenic CFU did not decrease in number during the 15 days of hypoxia, indeed, they both revealed cyclic increases. These results are discussed in terms of CFU kinetics and humoral mediation.