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

Science  19 Sep 2014:
Vol. 345, Issue 6203, pp. 1509-1512
DOI: 10.1126/science.1256337

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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

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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