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The bgJ/bgJ:W/WV bone marrow chimera. A model for studying stem cell regulation.

In studies with bgJ/bgJ:W/WV chimeric mice, we used the biege neutrophil marker as a criterion of of W/WV marrow replacement by implanted bgJ/bg/J stem cells. Data from a 50-fold range of inoculum doses and a 2-year period of observation indicate a hyperbolic pattern of replacement expressed as a log dose-response relationship. The saturating effect with increasing inoculum dose was interpreted as reflecting random initial stem cell seeding in bone marrow coupled with a decreasing efficiency of colonization by migration. From the statistics of random sampling and the exponential decrease of the 63% replacement dose with time, we estimate that W/WV marrow contains about 2600 stem cell regulatory volumes of about 10(8) mu3 (50 cell diameters) each, a dimension consistent with concepts of short-range cell-cell interactions. Our observations suggest that each regulatory volume is essentially self-contained and that stem cell migration is generally restricted to contiguous volumes.