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Science. 2014 Sep 19;345(6203):1509-12. doi: 10.1126/science.1256337.

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

Author information

  • 1Molecular Genetics of Stem Cells Laboratory, Institute of Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, QC, Canada.
  • 2Medicinal Chemistry, IRIC, University of Montreal, Montreal, QC, Canada.
  • 3Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.
  • 4Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada.
  • 5Division of Hematology, Maisonneuve-Rosemont Hospital, Montreal, QC, Canada. Department of Medicine, Faculty of Medicine, Université de Montreal, Montreal, QC, Canada.
  • 6Clinical Research Division, Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA, USA.
  • 7Clinical Research Division, Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA, USA. Department of Medicine and Pathology, University of Washington, Seattle, WA, USA.
  • 8Ontario Cancer Institute, University Health Network, Toronto, ON, Canada.
  • 9Ontario Cancer Institute, University Health Network, Toronto, ON, Canada. Department of Immunology, University of Toronto, Toronto, ON, Canada.
  • 10Molecular Genetics of Stem Cells Laboratory, Institute of Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, QC, Canada. Division of Hematology, Maisonneuve-Rosemont Hospital, Montreal, QC, Canada. Department of Medicine, Faculty of Medicine, Université de Montreal, Montreal, QC, Canada. guy.sauvageau@umontreal.ca.

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.

Copyright © 2014, American Association for the Advancement of Science.

PMID:
25237102
[PubMed - indexed for MEDLINE]
PMCID:
PMC4372335
Free PMC Article
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