ENHANCED EXPANSION OF CULTURED HEMATOPOIETIC STEM

对于临床造血抑制患者， 自体造血干细胞（HSC），其可以被操作， 在文化上的扩展会非常有益。然而，原始HSC与 多能潜能和长期繁殖能力目前是 很难在文化中维持;他们倾向于成熟成血统- 忠诚的祖先本提案的长期目标是 表明最近表征的哺乳动物蛋白Cyr 61， 其重组形式可以大量纯化， 增强培养物中多能人HSC的扩增。短期 目的是研究小鼠Cyr 61是否可以作为补充剂发挥作用， 鼠HSC培养系统。的具体目标和设计 该项目将建立长期的小鼠HSC培养物， 没有补充Cyr 61，并测定这些培养物的群体 生长速度，以及未成熟干细胞的相对比例等 成熟的祖细胞Cyr 61增强细胞增殖能力的证明 HSC在培养物中的扩增将导致尝试使用这些细胞来 在II期中影响体内造血重建。

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.