INDUCIBLE AMPLICATION OF HEMATOPOIETIC STEM CELLS

造血干细胞的诱导扩增

• 批准号: 2699187
• 负责人: R EPSTEIN-BAAK
• 金额: --
• 依托单位: AVANIR PHARMACEUTICALS
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-20 至 1997-08-20
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2699187
• 关键词: INDUCIBLE; AMPLICATION; HEMATOPOIETIC; STEM; CELLS

A strategy for expanding hematopoietic stem cells and early lineage- committed progenitors has been described. The oncogenic mutant of the H- ras gene which can induce proliferation in hematopoietic cells has been cloned into a vector containing the regulatory elements of the TN10 operon. The gene can be temporally regulated in a reversible manner. Hence the targeted cells can be expanded in the presence of an inducer (tetracycline). once a significant increase in the number of cells is attained, the inducer is removed in order that the amplified cells can revert to a normal phenotype. Amplification procedures have been outlined that will allow the characterization of cells which proliferate in response to activated ras. The cells can than be evaluated for their ability to reconstitute SCID mice. It is hoped that reconstitution of humans can then be contemplated, once a further fail-safe mechanism that mediates excision of the inserted gene is introduced. The cells thus amplified will also be available for basic research directed at determining additional means of regulating proliferation with the purpose of further expansion of progenitor and lineage precursors.

一种扩增造血干细胞和早期谱系的策略 已经描述了承诺的祖细胞。 H-的致癌突变体 ras基因可诱导造血细胞增殖， 克隆到含有TN 10操纵子调控元件的载体中。 该基因可以以可逆的方式进行时间调节。 因此 靶细胞可以在诱导剂存在下扩增 （四环素）。 一旦细胞数量显著增加， 获得时，去除诱导物，以便扩增的细胞可以 恢复到正常的表型。 扩增程序已概述 这将使细胞的特性， 激活RAS。 然后可以评估细胞的能力， 重组SCID小鼠。 希望人类的重建能够 一旦进一步的故障安全机制，介导切除， 插入的基因被引入。 如此扩增的细胞也将被 可用于基础研究，旨在确定 管制扩散，目的是进一步扩大 祖先和谱系前体。