Depletion of reserve in the hemopoietic system: I. Self-replication by stromal cells related to chronologic age.

Transplanted devascularized mouse femurs and spleens or spleens ligated in situ all undergo a period of massive necrosis followed by a period of cellular regeneration and reconstitution of tissue components. This renewal of stromal tissue is endogenous to the organ and proliferates inward from a thin rim of surviving cells. Components of the femoral or splenic stroma constitute a hemopoietic microenvironment whose functions include the lodgment, commitment to differentiation and support of the proliferation of hemopoietic stem cells and their differentiating descendents. By using measures of the ability to support hemopoiesis, and the histological appearance of the reconstituted hemopoietic organs, it was shown that the degree of regeneration of the stroma was inversely related to its chronological age. Thus, although age-related changes in stromal cells are not readily demonstrable in hemopoietic tissue during a normal lifespan, they are in process and can be made obvious under anoxic conditions causing cell death followed by an unusual demand for cell replication. Key cellular components of such aged tissues apparently have either lessened resistance to anoxia or a reduction in replicative potential or both. The second alternative interpretation suggests an analogy in vivo to mesenchymal-cell clonal attenuation observed in vitro.