CORD BLOOD EXPANSION: Pyrimidoindole derivatives are agonists of human hematopoietic stem cell self-renewal.
Fares, Iman 1; Chagraoui, Jalila 1; Gareau, Yves 2; Gingras, Stephane 2; Ruel, Rejean 2; Mayotte, Nadine 1; Csaszar, Elizabeth 3; Knapp, David J. H. F. 4; Miller, Paul 4; Ngom, Mor 4; Imren, Suzan 4; Roy, Denis-Claude 5,6; Watts, Kori L. 7; Kiem, Hans-Peter 7,8; Herrington, Robert 9; Iscove, Norman N. 9,10; Humphries, Keith R. 4; Eaves, Connie J. 4; Cohen, Sandra 5,6; Marinier, Anne 2; Zandstra, Peter W. 3; Sauvageau, Guy 1,5,6,*
[Report]
Science.
345(6203):1509-1512, September 19, 2014.
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: 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.
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