ENHANCED EXPANSION OF CULTURED HEMATOPOIETIC STEM

对于临床上有造血抑制的患者，介绍 自体造血干细胞(HSC)可以被操纵和 在文化上的扩展将是非常有益的。但是，原始HSC具有 多潜能和长期再生能力是目前 很难在文化中维持；他们往往会成熟为世系- 忠诚的祖先。这项提议的长期目标是 证明了最近鉴定的哺乳动物蛋白Cyr61，a 其重组形式可以大量纯化，将 促进人多能干细胞在培养中的扩增。短期内 目的是研究小鼠Cyr61是否可以作为补充 小鼠的HSC培养系统。该项目的具体目标和设计 该项目将建立长期的小鼠HSC培养或 不添加Cyr61，并对这些培养物的种群进行分析 关于生长率，以及未成熟干细胞的相对比例等 成熟的祖先。Cyr61增强能力的演示 在培养中扩增HSC将导致尝试使用这些细胞来 二期对体内造血细胞再增殖的影响。

For clinical patients with suppressed hematopoiesis, introduction of autologous hematopoietic stem cells (HSC) that can be manipulated and expanded in culture would be very beneficial. However, primitive HSC with pluripotent potential and long term repopulating ability are presently difficult to maintain in culture; they tend to mature into lineage- committed progenitors. The long term goal of this proposal is to demonstrate that the recently characterized mammalian protein Cyr61, a recombinant form of which can be purified in large quantities, will enhance expansion of pluripotent human HSC in culture. The short term goal is to investigate whether murine Cyr61 can function as a supplement to a murine HSC culture system. The specific aims and design of the project will be to establish long term murine HSC cultures with or without supplemental Cyr61, and assay the populations of these cultures for growth rate, and relative proportions of immature stem cells and more mature progenitors. Demonstration of the ability of Cyr61 to enhance expansion of HSC in culture would lead to attempts to use these cells to effect in vivo hematopoietic repopulation in Phase II.