An in vitro investigation of the hematopoietic microenvironment in young and aged mice.

Dexter-type cultures derived from the bone marrow of young and aged mice were established as in vitro correlates to the hematopoietic microenvironment and inoculated two weeks later with fresh bone marrow-derived stem cells (colony-forming units, CFUs) from young, syngeneic mice. Such cultures allowed the observation, quantitation and evaluation of interactions between aged or young microenvironments and the young stem cells. The hematopoietic microenvironments derived from aged marrow were found to support a greater total nucleated cellularity and a significantly greater number of CFUs. Also, the production of CFUs on aged monolayers occurred at an elevated rate. Though cyclic variations in total cellularity were noted in all cultures, the granulocyte--macrophage lineage always predominated. Lymphocyte populations in all cultures were seen to decline rapidly with time as other cell types became more abundant. The number of megakaryocytes in the aged marrow-derived cultures was significantly elevated in the early time periods post-refeeding. Differences in the adherent cell population densities were noted with the aged monolayers being somewhat less dense. However, there were no differences in morphologically identifiable cell types comprising the adherent layers derived from marrow of young and old mice. From these results, we conclude that there are differences in the ability of aged versus young hematopoietic microenvironments to support normal young stem cells in vitro and that the microenvironmental influences present in the in vitro system are reflective of those seen in the in vivo marrow microenvironment.