Cord blood expansion. Pyrimidoindole derivatives are agonists of human hematopoietic stem cell self-renewal.

Fares, Iman; Chagraoui, Jalila; Gareau, Yves; Gingras, Stéphane; Ruel, Réjean; Mayotte, Nadine; Csaszar, Elizabeth; Knapp, David J H F et al. · Science · 2014

basic_science · Level V

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Abstract

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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