Femoral bone marrow curettage produced an intense stimulus on hematopoietic stem cells (HSC) in sublethally irradiated mice 4 days after curettage. A similar but lesser stimulation of 59Fe incorporation into spleen and red cells was observed. Previous investigations have shown that this effect is not observed in unirradiated mice. Histologic studies of the curetted femurs indicated a rapid regeneration of a primitive mesenchymal tissue within the medullary cavities during the period of stimulation. It is suggested that the primitive mesenchymal cells synthesize a humoral factor that is capable of stimulating HSC in a marrow microenvironment of depleted cellularity. The observations are consistent with a hypothesis of inhibition of HSC response to a similar stimulus in a normocellular marrow by a mechanism of cell-cell interaction. The humoral factor affects HSC similar to fetuin, spleen extract, and alpha globulin fractions.

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