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

Abstract

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. PMID: 20688981 Funding information This work was supported by: NIEHS NIH HHS, United States Grant ID: R01 ES007685-11 NIEHS NIH HHS, United States Grant ID: P42 ES004699-24 NIEHS NIH HHS, United States Grant ID: R01 ES004869 NIEHS NIH HHS, United States Grant ID: ES004869 NIEHS NIH HHS, United States Grant ID: ES04699 NIEHS NIH HHS, United States Grant ID: R01 ES004869-23 NIEHS NIH HHS, United States Grant ID: P42 ES004699 NIEHS NIH HHS, United States Grant ID: ES007685 NIEHS NIH HHS, United States Grant ID: R01 ES007685 More Less keyboard_arrow_down

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