The use of Hematopoietic Growth Factors in Healthy Subjects

造血生长因子在健康受试者中的应用

基本信息

批准号：
7733567
负责人：
David Frank Stroncek
金额：
$ 3.94万
依托单位：
CLINICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

项目摘要

Granulocyte colony-stimulating factor (G-CSF) is the standard growth factor for mobilizing hematopoietic progenitor cells in healthy peripheral blood progenitor cell (PBPC) donors. G-CSF is given daily for 5 days to PBPC donors prior collecting PBPC concentrates by apheresis. PBPC donors given G-CSF experience splenic enlargement and, rarely, spontaneous rupture of the spleen. The magnitude of spleen length increase is highly varialbe among individuals and is not affected by donor gender, race, or age. We are currently investigating the mechanisms of G-CSF mobilization of stem cells into the peripheral blood. Plasma protein profiles are being compared before and after G-CSF administration. Associations between the expression of cell adhesion molecules on mature neutrophils and neutrophil precursors and spleen size change will also be investigated. An agent that mobilizes stem cells by a different mechanism than G-CSF is also being used clinically to mobilize stem cells. This agent, AMD3100, mobilizes stem cells within a few hours after it is given by directly disrupting the binding of CXCR4 on stem cells with SDF-1 or CXCL12 on marrow storma. In constract, G-CSF mobilizes stem cells after it has been given for 4 to 5 days by the release of proteolytic enzymes that degrade adhesion molecule and by the down-regulation of expression of adhesion molecules. Prelimenary data suggests that stem cells mobilized by AMD3100 and G-CSF have different properties and functions. We have begun to investigate differences in hematopoietic stem cells mobilized by AMD3100 and G-CSF using different gene expression microarrays and micro RNA expression microarrays.

粒细胞刺激因子（G-CSF）是动员健康外周血祖细胞（PBPC）供体中造血祖细胞的标准生长因子。 G-CSF每天给PBPC捐赠者进行5天的时间，以前通过放置良心收集PBPC浓缩物。给予G-CSF的PBPC供体经历了脾脏增大，并且很少发生脾脏的自发破裂。脾脏长度增加的大小在个体中高度差异，并且不受捐赠者性别，种族或年龄的影响。我们目前正在研究将干细胞动员G-CSF动员到外周血中的机制。在G-CSF给药前后，正在比较血浆蛋白谱。还将研究细胞粘附分子在成熟中性粒细胞和中性粒细胞前体和脾脏大小变化之间的关联。通过与G-CSF不同机制动员干细胞的药物也在临床上用于动员干细胞。该试剂AMD3100在给出干细胞后几个小时内动员了CXCR4在干细胞上与SDF-1或CXCL12在Marrow Storma上的结合。在Contract中，G-CSF通过释放蛋白水解酶释放降解粘附分子并通过下调粘附分子的表达来动员4至5天。初步数据表明，由AMD3100和G-CSF动员的干细胞具有不同的特性和功能。我们已经开始研究使用不同的基因表达微阵列和微RNA表达微阵列动员AMD3100和G-CSF的造血干细胞的差异。