ETIOLOGY, PATHOGENESIS AND TREATMENT OF APLASTIC ANEMIA

再生障碍性贫血的病因、发病机制和治疗

• 批准号: 3342980
• 负责人: MALCOLM A. MOORE
• 金额: $ 14.19万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-09-30 至 1986-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3342980
• 关键词: aplastic anemia; colony stimulating factor; ferritin; flow cytometry; hematopoietic growth factor; hematopoietic stem cells; histochemistry /cytochemistry; histocompatibility antigens; human tissue; immune adherence reaction; immunochemistry; immunohematology; immunoregulation; interleukin 2; mixed tissue /cell culture; monoclonal antibody; prostaglandin E; suppressor T lymphocyte; tissue /cell culture

The pathophysiology of aplastic anemia remains obscure but bone marrow transplantation and more recently therapy with anti-thymocyte or anti-lymphocyte globulin have proved clinically effective. This research program is designed to investigate the role of suppressor cells in so-called "immune" aplastic anemia, to determine the phenotypic characteristics of such cells using a panel of monoclonal antibodies, to amplify autoreactive cells using Interleukin 2 and to determine the nature of the cell population being suppressed. Attention will be directed at suppressor mechanisms acting upon accessory cells producing hematopoietic growth regulatory factors such as colony stimulating factors or inhibitory activities such as acidic isoferritin. Assays for pluripotential stem cells, both clonal and in suspension culture, will be used to detect suppressor cells and regulatory factor dysfunction where the primary target is the stem cell. An additional objective is to define the role of the human bone marrow microenvironmental cells on the proliferation and differentiation of hematopoietic stem cells using marrow from untreated aplastics and from patients recovering from bone marrow transplantation or ATG therapy. Well defined in vitro assays will be employed to assess the changes occurring in the number and hemopoietic function of marrow fibroblasts, endothelial cells, adipocytes and macrophage-derived lipid containing cells. Analysis of these changes will allow determination of 1) aplasia primarily due to environmental defects; 2) aplasia due to autoreactive cells compromising microenvironmental function; 3) the influence of immunosuppression and/or cytoreduction or transplantation on the integrity of the microenvironment.

再生障碍性贫血的病理生理机制仍不清楚，但骨髓 移植和最近的抗胸腺细胞治疗， 抗淋巴细胞球蛋白已被证明在临床上有效。 本研究 该计划旨在研究抑制细胞在 所谓的“免疫性”再生障碍性贫血，以确定表型 使用一组单克隆抗体对这些细胞的特征进行分析， 用白细胞介素2扩增自身反应性细胞， 细胞数量受到抑制的可能性 请注意， 抑制机制作用于辅助细胞产生造血 生长调节因子如集落刺激因子或抑制因子 活性如酸性异铁蛋白。 多能干细胞的测定 细胞，克隆和悬浮培养，将用于检测 抑制细胞和调节因子功能障碍， 就是干细胞 另一个目标是确定 人骨髓微环境对细胞增殖和 使用未经治疗的骨髓分化造血干细胞 再生障碍和从骨髓移植中恢复的患者，或 ATG疗法。 将采用明确定义的体外试验来评估 骨髓数量和造血功能的变化 成纤维细胞、内皮细胞、脂肪细胞和巨噬细胞衍生的脂质 包含细胞。 对这些变化的分析将允许确定1） 发育不全主要是由于环境缺陷; 2）发育不全由于 自身反应细胞损害微环境功能; 3） 免疫抑制和/或细胞减少或移植对 微环境的完整性。