Spatial organisation of CFU-S proliferation regulators in the mouse femur.

CFU-S proliferation can be regulated by an inhibitor and a stimulator which are produced locally in the bone marrow. The spatial distribution of cells elaborating these factors has been studied by separating marrow, zonally, into axial, marginal and bone-associated fractions and further separating the inhibitor and stimulator producing cells from these fractions by means of density cuts in bovine serum albumin. The inhibitor- and stimulator-producing cells are found respectively in bands of density less than 1.064 g/cm3 and 1.064-1.072 g/cm2. Factors synthesised by these individual fractions were assayed for their ability to inhibit or stimulate CFU-S proliferation by thymidine suicide measurements. Axial cells contain a high concentration of inhibitor-producing cells but the marginal and bone fractions contain relatively few. Stimulator-producing cells have a very sharp gradient in the opposite direction with an extremely high concentration in the vicinity of the bone surface. These distributions fit with those of CFU-S proliferation and of fibroblastoid-CFC suggesting that the inhibitor-producing cell is an integral part of the micro-environment which maintains the stem cell's capacities while the stimulator-producing cell may be more closely associated with the differentiation processes which take place closer to the bone surface.