Studies on regulation of hematopoieses by bone marrow stromal cells

1. 骨髓基质细胞包括成纤维细胞、脂肪细胞和内皮细胞，它们对造血干细胞的分化和增殖有影响。从10名健康志愿者和10名急性白血病、6名慢性骨髓性白血病和10名再生障碍性贫血患者中获得骨髓成纤维细胞和脂肪细胞。脐带静脉内皮细胞培养。从这些基质细胞中获得条件培养基。研究表明，成纤维细胞通过细胞间相互作用和细胞介导的液体因子调节颗粒形成。认为急性白血病和再生障碍性贫血的粒细胞减少是由于成纤维细胞对粒细胞生成的调节受到干扰所致，慢性粒细胞白血病的白细胞增多是由于成纤维细胞对粒细胞生成的抑制因子功能障碍所致。脂肪细胞不影响颗粒生成。内皮细胞是释放粒细胞集落刺激因子的重要细胞。成纤维细胞抑制红细胞生成，但从成纤维细胞中获得的脂肪细胞与类固醇激素孵育不抑制红细胞生成。再生障碍性贫血患者的成纤维细胞比正常人更能抑制红细胞生成，而再生障碍性贫血患者的脂肪细胞从抑制中恢复的程度也明显大于正常人成纤维细胞抑制巨核细胞和混合髓系结落形成。脂肪细胞和内皮细胞不影响这些集落的形成从成纤维细胞条件培养基中获得的抑制因子是耐热的，其分子量为1X10^4 ~ 5X10^4道尔顿这些结果表明，不同成分的骨髓间质细胞如成纤维细胞对骨髓造血有不同的影响，这对了解急性白血病和再生障碍性贫血的发病机制有重要意义。

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.