Publication Date:
2014-09-23
Description:
The small number of hematopoietic stem and progenitor cells in cord blood units limits their widespread use in human transplant protocols. We identified a family of chemically related small molecules that stimulates the expansion ex vivo of human cord blood cells capable of reconstituting human hematopoiesis for at least 6 months in immunocompromised mice. The potent activity of these newly identified compounds, UM171 being the prototype, is independent of suppression of the aryl hydrocarbon receptor, which targets cells with more-limited regenerative potential. The properties of UM171 make it a potential candidate for hematopoietic stem cell transplantation and gene therapy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372335/" 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/PMC4372335/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fares, Iman -- Chagraoui, Jalila -- Gareau, Yves -- Gingras, Stephane -- Ruel, Rejean -- Mayotte, Nadine -- Csaszar, Elizabeth -- Knapp, David J H F -- Miller, Paul -- Ngom, Mor -- Imren, Suzan -- Roy, Denis-Claude -- Watts, Kori L -- Kiem, Hans-Peter -- Herrington, Robert -- Iscove, Norman N -- Humphries, R Keith -- Eaves, Connie J -- Cohen, Sandra -- Marinier, Anne -- Zandstra, Peter W -- Sauvageau, Guy -- HL84345/HL/NHLBI NIH HHS/ -- R01 HL084345/HL/NHLBI NIH HHS/ -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2014 Sep 19;345(6203):1509-12. doi: 10.1126/science.1256337.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Genetics of Stem Cells Laboratory, Institute of Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, QC, Canada. ; Medicinal Chemistry, IRIC, University of Montreal, Montreal, QC, Canada. ; Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada. ; Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada. ; Division of Hematology, Maisonneuve-Rosemont Hospital, Montreal, QC, Canada. Department of Medicine, Faculty of Medicine, Universite de Montreal, Montreal, QC, Canada. ; Clinical Research Division, Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA, USA. ; Clinical Research Division, Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA, USA. Department of Medicine and Pathology, University of Washington, Seattle, WA, USA. ; Ontario Cancer Institute, University Health Network, Toronto, ON, Canada. ; Ontario Cancer Institute, University Health Network, Toronto, ON, Canada. Department of Immunology, University of Toronto, Toronto, ON, Canada. ; Molecular Genetics of Stem Cells Laboratory, Institute of Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, QC, Canada. Division of Hematology, Maisonneuve-Rosemont Hospital, Montreal, QC, Canada. Department of Medicine, Faculty of Medicine, Universite de Montreal, Montreal, QC, Canada. guy.sauvageau@umontreal.ca.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25237102" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cell Culture Techniques
;
Fetal Blood/cytology/*drug effects/physiology
;
Genetic Therapy/methods
;
Hematopoiesis/*drug effects/physiology
;
Hematopoietic Stem Cell Transplantation/methods
;
Hematopoietic Stem Cells/*drug effects/physiology
;
Humans
;
Immunocompromised Host
;
Indoles/chemistry/*pharmacology
;
Mice
;
Pyrimidines/chemistry/*pharmacology
;
Receptors, Aryl Hydrocarbon/*antagonists & inhibitors
;
Regeneration/*drug effects
;
Small Molecule Libraries/chemistry/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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