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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

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

PMID:
25237102
PMCID:
PMC4372335
DOI:
10.1126/science.1256337
[Indexed for MEDLINE]
Free PMC Article

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