DEVELOPMENT OF HUMAN MEGAKARYOCYTE PROGENITOR ASSAY

人类巨核细胞祖细胞检测的开发

• 批准号: 2070000
• 负责人: MARTIN J MURPHY
• 金额: $ 36.76万
• 依托单位: HIPPLE CANCER RESEARCH CORPORATION
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 1996-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2070000
• 关键词: CD antigens; antiAIDS agent; antineoplastics; bioassay; cell differentiation; cytotoxicity; deficient growth media; drug screening /evaluation; flow cytometry; human tissue; megakaryocytes; method development; monoclonal antibody; thrombocytopenia; thrombopoiesis; tissue /cell culture

DESCRIPTION: Since thrombocytopenia is a serious life threatening complication of cancer and AIDS chemotherapy, standardized and optimized human assays for human megakaryocyte progenitors would be useful for determining and/or predicting the toxicity of experimental chemotherapeutic drugs. The proposed experiments in this Phase II application use megakaryocyte and stem cell populations isolated by FACS and analyzed by flowcytometry to evaluate the toxicity of anticancer and anti HIV drugs on megakaryocytes and their progenitors. The mechanism of drug toxicity will be explored using these cells to distinguish whether the toxic effects of the drugs are due to a direct effect on megakaryocytes or on more primitive hematopoietic precursor cells. The in vitro toxicity data will be correlated with in vivo toxicity data from patients who receive the same drugs.This will enable a determination of the predictive accuracy of the in vitro data in the same way that drug toxicity to CFU GM and CFU E/BFU E has been shown to correlate with in vivo myelotoxicity using assays developed at Hipple Cancer Research Center. In addition, the Investigators propose to test for drug toxicity using long term bone marrow cultures as an in vitro model of steady stay hematopoiesis. This system is proposed to allow the capability of identifying the mechanisms underlying early versus late onset thrombocytopenia. In addition, the proposed research may provide methods for optimal growth of primitive hematopoietic cells and for selecting the optimal drug combination for mobilizing bone marrow stem cells to the peripheral blood for clinical transplantation, predictions which can be tested clinically.

描述：由于血小板减少症是严重危及生命的 癌症和艾滋病化疗并发症，标准化和优化 人巨核细胞祖细胞的人测定可用于 确定和/或预测实验性药物的毒性 化疗药物 第二阶段的拟议实验 本申请使用巨核细胞和干细胞群， 流式细胞仪分析，以评估 抗癌和抗HIV药物对巨核细胞及其祖细胞的作用。 将利用这些细胞探索药物毒性的机制 以区分药物的毒性作用是否是由于 对巨核细胞或更原始造血细胞的直接影响 前体细胞 体外毒性数据将与以下数据相关： 接受相同药物的患者的体内毒性数据 这将使得能够确定药物的预测准确性。 体外试验结果表明，药物对CFU GM和CFU的毒性 E/BFU E已被证明与体内骨髓毒性相关， 在Hipple癌症研究中心开发的测定。 此外该 研究人员建议使用长期骨测试药物毒性 骨髓培养物作为稳态造血的体外模型。 这 系统被提议允许识别机制的能力 基础早发性与晚发性血小板减少症。 此外，本发明还提供了一种方法， 拟议的研究可以提供优化增长的方法， 原始造血细胞和选择最佳药物 用于将骨髓干细胞动员到 外周血临床移植，预测，可以 进行临床测试。