INDUCIBLE AMPLICATION OF HEMATOPOIETIC STEM CELLS

造血干细胞的诱导扩增

• 批准号: 2357777
• 负责人: R EPSTEIN-BAAK
• 金额: $ 9.99万
• 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
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2357777
• 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血统的策略- 忠诚的祖先已经被描述过了。H-的致癌突变体 可诱导造血细胞增殖的RAS基因已被 克隆到含有Tn10操纵子调控元件的载体中。 该基因可以以可逆的方式在时间上进行调节。因此， 靶细胞可以在诱导剂存在的情况下扩增 (四环素)。一旦细胞数量显著增加， 达到时，移除诱导剂，以便扩增的细胞可以 恢复到正常的表型。已概述了扩增程序 这将允许对作为反应而增殖的细胞进行表征 到激活的RAS。然后，可以评估这些细胞的能力 重建SCID小鼠。希望到那时，人类的重建可以 可以考虑，一旦有了另一种故障保护机制，就可以调解切除 对插入基因的克隆进行了初步研究。这样扩增的细胞也将被 可用于基础研究，旨在确定其他方法 管制扩散，目的是进一步扩大 祖先和血统的前身。