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Pyrimidoindole derivatives are agonists of human hematopoietic stem cell self-renewal

2014; American Association for the Advancement of Science; Volume: 345; Issue: 6203 Linguagem: Inglês

10.1126/science.1256337

1095-9203

Iman Fares, Jalila Chagraoui, Yves Gareau, Stéphane Gingras, Réjean Ruel, Nadine Mayotte, Elizabeth Csaszar, David J. H. F. Knapp, Paul H. Miller, Mor Ngom, Suzan Imren, Denis-Claude Roy, Kori L. Watts, Hans‐Peter Kiem, Robert Herrington, Norman N. Iscove, R. Keith Humphries, Connie J. Eaves, Sandra Cohen, Anne Marinier, Peter W. Zandstra, Guy Sauvageau,

T-cell and B-cell Immunology

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.