Publication Date:
2010-08-07
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033342/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033342/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- ES004869/ES/NIEHS NIH HHS/ -- ES007685/ES/NIEHS NIH HHS/ -- ES04699/ES/NIEHS NIH HHS/ -- P42 ES004699/ES/NIEHS NIH HHS/ -- P42 ES004699-24/ES/NIEHS NIH HHS/ -- R01 ES004869/ES/NIEHS NIH HHS/ -- R01 ES004869-23/ES/NIEHS NIH HHS/ -- R01 ES007685/ES/NIEHS NIH HHS/ -- R01 ES007685-11/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 2010 Sep 10;329(5997):1345-8. doi: 10.1126/science.1191536. Epub 2010 Aug 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20688981" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antigens, CD/analysis
;
Antigens, CD34/analysis
;
Aryl Hydrocarbon Hydroxylases/genetics/metabolism
;
Cell Count
;
Cell Lineage
;
Cell Proliferation
;
Cells, Cultured
;
Cytochrome P-450 CYP1B1
;
Cytokines/pharmacology
;
Glycoproteins/analysis
;
Hematopoiesis
;
*Hematopoietic Stem Cell Transplantation
;
Hematopoietic Stem Cells/cytology/drug effects/metabolism/*physiology
;
Humans
;
Mice
;
Mice, Inbred NOD
;
Mice, SCID
;
Multipotent Stem Cells/cytology/drug effects/physiology
;
Peptides/analysis
;
Purines/*metabolism/*pharmacology
;
Receptors, Aryl Hydrocarbon/*antagonists & inhibitors/metabolism
;
Signal Transduction
;
Small Molecule Libraries
;
Species Specificity
;
Tetrachlorodibenzodioxin/pharmacology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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