骨髓衰竭的病理机制及干预策略的基础研究

项目名称： 骨髓衰竭的病理机制及干预策略的基础研究

项目编号： No.81330015

项目类型： 重点项目

立项/批准年度： 2014

项目学科： 医药、卫生

项目作者： 韩忠朝

作者单位： 中国医学科学院

项目金额： 290万元

中文摘要： 骨髓衰竭在我国的发病率4倍于西方国家，严重危害着国人的健康，消耗了巨大的公共卫生资源。骨髓衰竭的确切发病机制不明，免疫抑制方案治疗骨髓衰竭其疗效似已达“顶峰”。因此，涉及骨髓衰竭的研究几乎涵盖实验血液学的重点领域。本项目拟从①造血干细胞生物学特征及其克隆性演变；②异常免疫反应（包括Th1和Th17淋巴细胞异常活化机制与Th22细胞相关因子）诱导的造血干细胞增殖衰竭；③间充质干细胞及其Toll样受体等方面探讨骨髓衰竭的病理机制，以期在骨髓衰竭基础研究领域取得突变；④同时建立骨髓衰竭期稳定、可操作性的骨髓衰竭动物模型，为研发、筛选及评估该类疾病的新型干预策略，如调节性T细胞和间充质干细胞在骨髓衰竭治疗中的疗效及安全性提供坚实的理论基础。

中文关键词： 骨髓衰竭;造血干细胞;克隆性演变;间充质干细胞;

英文摘要： Bone marrow failure is much more common in China compared to that in western countries, which represents a medical challenge for patients, physicians and the health authorities. The fundamental study to advance the current understandings of the pathological mechanisms and clinical practice of bone marrow failure involves almost all key point areas in the field of experimental hematology. The present study will focus on pathological mechanisms and novel curative strategies for bone marrow failure, including: ①The biological features and clonal evolution to myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) of hematopoietic stem cell from bone marrow failure patients; ② The abnormal immune mechanisms underlying bone marrow failure disorders; ③ The defects of mesenchyme stem cell and roles of toll-like receptors in bone marrow failure disorders; ④ Establishment of practical bone marrow failure animal models in order to develop novel therapeutic strategies, to evaluate the safety and efficacy of regulatory T cells (Treg) and mesenchyme stem cell for the treatment of bone marrow failure. Thus, our study will provide new insights into mechanisms of bone marrow failure and offer new strategies for the treatment of bone marrow failure.

英文关键词： Bone marrow failure;Hematopoietic stem cell;Clonal evolution;Mesenchyme stem cell