A bioactive designer cytokine for human hematopoietic progenitor cell expansion
A bioactive designer cytokine for human hematopoietic progenitor cell expansion
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DOI：
10.1038/nbt0297-142
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发表时间：
1997-02-01
影响因子：
46.9
通讯作者：
RoseJohn, S
中科院分区：
文献类型：
--
作者：
Fischer, M;Goldschmitt, J;RoseJohn, S
造血祖细胞的有效扩增至少需要同时刺激受体c-kit和gp 130，而c-kit由SCF激活;在不表达足够量IL-6 R的细胞中，gp 130可被可溶性IL-6 R（sIL-6 R）和IL-6的复合物激活。然而，IL-6/sIL-6 R的治疗用途，由于需要高浓度的sIL-6 R蛋白而受到阻碍，我们设计了一种由柔性肽链连接的sIL-6 R和IL-6的融合蛋白，该融合蛋白被高水平表达，在表达gp 130的细胞中，该融合蛋白在100：1时被证明是完全活性的，比未连接的IL-6和IL-6 R的组合低000倍的浓度。该融合蛋白用于以剂量依赖性方式有效地离体扩增人造血祖细胞。
Efficient expansion of hematopoietic progenitor cells requires, at least, the simultaneous stimulation of the receptors c-kit and gp130, While c-kit is activated by SCF; gp130, in cells which do not express sufficient amounts of IL-6R, can be activated by the complex of soluble IL-6R (sIL-6R) and IL-6, The therapeutic use of IL-6/sIL-6R, however, has been hampered by the high concentrations of the sIL-6R protein required, We have designed a fusion protein of sIL-6R and IL-6, linked by a flexible peptide chain, that was expressed to high levels, On gp130 expressing cells the fusion protein turned out to be fully active at 100 to 1,000-fold lower concentration than the combination of unlinked IL-6 and IL-6R. The fusion protein was used to effectively expand human hematopoietic progenitor cells ex vivo in a dose dependent fashion.