I. Fares, J. Chagraoui, Y. Gareau
Sep 19, 2014
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12
Influential Citations
398
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Science
Abstract
Human adult stem cell expansion Transfused blood saves lives. Despite the widespread use of this critical resource, it is difficult to increase blood cell numbers outside of the body. By screening thousands of small compounds, Fares et al. identify a molecule that expands human stem cell numbers in cord blood. The researchers generate many variations of that molecule and show that one such compound provides even greater human blood cell expansion. If researchers can provide increased numbers of stem cells and progenitor cells, cord blood should find even greater use in the clinic. Science, this issue p. 1509 The self-renewal of human hematopoietic stem cells in vitrois enhanced by the pyrimidoindole derivative UM171. 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.