Aryl Hydrocarbon Receptor Antagonists Promote the Expansion of Human Hematopoietic Stem Cells

Overview

Journal Science

Specialty Science

Date 2010 Aug 7

PMID 20688981

Citations 526

Authors

Anthony E Boitano

Jian Wang

Russell Romeo

Laure C Bouchez

Albert E Parker

Sue E Sutton

John R Walker

Colin A Flaveny

Gary H Perdew

Michael S Denison

Peter G Schultz

Michael P Cooke

Affiliations

Soon will be listed here.

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.

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