A model of intramedullary hematopoietic microenvironments based on stereologic study of the distribution of endocloned marrow colonies

Abstract

Hematopoietic colonies were studied in the marrow of alternate fraction-irradiated mice by light microscopic stereology to investigate the microenvironmental organization of marrow. Separate analyses of the relative colony cell density of undifferentiated, granulocytic, erythrocytic, and macrophage colonies in four marrow zones were carried out at 3, 4, and 5 days postirradiation (PI) for all colonies, all periarterial colonies, and all nonperiarterial colonies. The results demonstrate a differential colony cell distribution that does not appear to be due to a preferential distribution of certain colony types around arteries. Undifferentiated colony cells showed a consistent predilection for endosteal and periarterial regions, with the majority of colony cells occurring along bone. Erythrocytic colony cells proliferated initially in intermediate and central marrow zones and along arteries. Granulocytic colony cells occurred in all areas at 3 days PI, but increased in density along bone thereafter. Macrophage colony cells occurred in all zones at 4 days PI, but at 5 days were concentrated in subosteal and central regions. Macrophage colonies also occurred periarterially. To explain these findings and the organization of normal bone marrow, we present a detailed model of the microenvironmental organization of intramedullary hematopoiesis. This model portrays the stroma as engendering distinct microenvironments for stem cell replication, stem cell commitment, and early progenitor cell proliferation.