Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Science. 2010 Sep 10;329(5997):1345-8. doi: 10.1126/science.1191536. Epub 2010 Aug 5.
Although practiced clinically for more than 40 years, the use of hematopoietic stem cell (HSC) transplants remains limited by the ability to expand these cells ex vivo. An unbiased screen with primary human HSCs identified a purine derivative, StemRegenin 1 (SR1), that promotes the ex vivo expansion of CD34+ cells. Culture of HSCs with SR1 led to a 50-fold increase in cells expressing CD34 and a 17-fold increase in cells that retain the ability to engraft immunodeficient mice. Mechanistic studies show that SR1 acts by antagonizing the aryl hydrocarbon receptor (AHR). The identification of SR1 and AHR modulation as a means to induce ex vivo HSC expansion should facilitate the clinical use of HSC therapy.
虽然造血干细胞 (HSC) 移植在临床上已经应用了 40 多年，但由于其体外扩增能力有限，其应用仍然受到限制。一项针对原代人 HSCs 的无偏筛选发现，嘌呤衍生物 StemRegenin 1 (SR1) 可促进 CD34+细胞的体外扩增。用 SR1 培养 HSCs 可使表达 CD34 的细胞增加 50 倍，保持植入免疫缺陷小鼠能力的细胞增加 17 倍。机制研究表明，SR1 通过拮抗芳香烃受体 (AHR) 发挥作用。鉴定 SR1 和 AHR 调节作为诱导体外 HSC 扩增的一种手段，应有助于 HSC 治疗的临床应用。
