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

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

Research output: Contribution to journalArticle

560 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1345-1348
Number of pages4
JournalScience
Volume329
Issue number5997
DOIs
StatePublished - Sep 10 2010

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Aryl Hydrocarbon Receptors
Hematopoietic Stem Cells
Cell- and Tissue-Based Therapy
Transplants
StemRegenin 1

All Science Journal Classification (ASJC) codes

  • General

Cite this

Boitano, A. E., Wang, J., Romeo, R., Bouchez, L. C., Parker, A. E., Sutton, S. E., ... Cooke, M. P. (2010). Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells. Science, 329(5997), 1345-1348. https://doi.org/10.1126/science.1191536
Boitano, Anthony E. ; Wang, Jian ; Romeo, Russell ; Bouchez, Laure C. ; Parker, Albert E. ; Sutton, Sue E. ; Walker, John R. ; Flaveny, Colin A. ; Perdew, Gary H. ; Denison, Michael S. ; Schultz, Peter G. ; Cooke, Michael P. / Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells. In: Science. 2010 ; Vol. 329, No. 5997. pp. 1345-1348.
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Boitano, AE, Wang, J, Romeo, R, Bouchez, LC, Parker, AE, Sutton, SE, Walker, JR, Flaveny, CA, Perdew, GH, Denison, MS, Schultz, PG & Cooke, MP 2010, 'Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells', Science, vol. 329, no. 5997, pp. 1345-1348. https://doi.org/10.1126/science.1191536

Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells. / Boitano, Anthony E.; Wang, Jian; Romeo, Russell; Bouchez, Laure C.; Parker, Albert E.; Sutton, Sue E.; Walker, John R.; Flaveny, Colin A.; Perdew, Gary H.; Denison, Michael S.; Schultz, Peter G.; Cooke, Michael P.

In: Science, Vol. 329, No. 5997, 10.09.2010, p. 1345-1348.

Research output: Contribution to journalArticle

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AU - Cooke, Michael P.

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Boitano AE, Wang J, Romeo R, Bouchez LC, Parker AE, Sutton SE et al. Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells. Science. 2010 Sep 10;329(5997):1345-1348. https://doi.org/10.1126/science.1191536