Studies on regulation of hematopoieses by bone marrow stromal cells

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1. It has been investigated that bone marrow stromal cells consisting of fibroblasts, fat cells and endothelial cells influence the differentiation and proliferation of hematopoietic stem cells. Bone marrow fibroblasts and fat cells were obtained from 10 healthy volunteers and patients with 10 acute leukemia, six chronic mylogenous leukemia and 10 aplastic anemia. Endothelial cells cultured from umbilical cord veins. Conditines-medium was obtained from these stromal cells.2. It has been revealed that fibroblasts regulate granulopoiesis with cell-to-cell interaction and cell-mediated liquid factor. It is considered that granulocytopenia in acute leukemia and aplastic anemia is due to disturbed regulation of granulopoiesis by fibroblasts and that leukocytosis in chronic myelogenous leukemia is due to dysfunction of inhibitory factor of fibroblasts on granulopoiesis. Fat cells did not influence granulopoiesis. Endothelial cells proved importaht cells which release granulocyte colony-stimulating factor.3. Fibroblasts inhibited erythropoiesis, but fat cells obtained from fibroblasts incubated with steroid hormone did not inhibit erythropoiesis. Fibroblasts derived from patients with aplastic anemia inhibited erythropoiesis to a greater extent than those from normal subjects and the degree of recovery from inhibition by fat cells from the patients was significantly greater than those from normal individuals.4 Fibroblasts inhibited megakaryocyte and mixed myeloid lineage colont formation. Fat cells and endothelial cells did not influence these colony formations.5 The inhibitory factor obtained from fibroblast conditioned-medium was heat-resistant and its molecuar weight was 1X10^4 - 5X10^4 dalton.6 These results show that different components of stromal cells such as fibroblasts have contrasting effects on hematopoiesis in the bone marrow and they are useful findings for unerstanding pathogenesis of acute leukemia and aplastic anemia.