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Publication : Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells.

First Author  Boitano AE Year  2010
Journal  Science Volume  329
Issue  5997 Pages  1345-8
PubMed ID  20688981 Mgi Jnum  J:167433
Mgi Id  MGI:4868285 Doi  10.1126/science.1191536
Citation  Boitano AE, et al. (2010) Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells. Science 329(5997):1345-8
abstractText  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.
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