title: Cord blood expansion. Pyrimidoindole derivatives are agonists of human hematopoietic stem cell self-renewal.
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.
authors.affiliation: Molecular Genetics of Stem Cells Laboratory, Institute of Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, QC, Canada.
authors.forename: Iman
authors.initials: I
authors.lastname: Fares
authors.affiliation: Molecular Genetics of Stem Cells Laboratory, Institute of Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, QC, Canada.
authors.forename: Jalila
authors.initials: J
authors.lastname: Chagraoui
authors.affiliation: Medicinal Chemistry, IRIC, University of Montreal, Montreal, QC, Canada.
authors.forename: Yves
authors.initials: Y
authors.lastname: Gareau
authors.affiliation: Medicinal Chemistry, IRIC, University of Montreal, Montreal, QC, Canada.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Gingras
authors.affiliation: Medicinal Chemistry, IRIC, University of Montreal, Montreal, QC, Canada.
authors.forename: Réjean
authors.initials: R
authors.lastname: Ruel
authors.affiliation: Molecular Genetics of Stem Cells Laboratory, Institute of Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, QC, Canada.
authors.forename: Nadine
authors.initials: N
authors.lastname: Mayotte
authors.affiliation: Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Csaszar
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada.
authors.forename: David J H F
authors.initials: DJ
authors.lastname: Knapp
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Miller
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada.
authors.forename: Mor
authors.initials: M
authors.lastname: Ngom
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada.
authors.forename: Suzan
authors.initials: S
authors.lastname: Imren
authors.affiliation: Division of Hematology, Maisonneuve-Rosemont Hospital, Montreal, QC, Canada. Department of Medicine, Faculty of Medicine, Université de Montreal, Montreal, QC, Canada.
authors.forename: Denis-Claude
authors.initials: DC
authors.lastname: Roy
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA, USA.
authors.forename: Kori L
authors.initials: KL
authors.lastname: Watts
authors.affiliation: 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.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Kiem
authors.affiliation: Ontario Cancer Institute, University Health Network, Toronto, ON, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Herrington
authors.affiliation: Ontario Cancer Institute, University Health Network, Toronto, ON, Canada. Department of Immunology, University of Toronto, Toronto, ON, Canada.
authors.forename: Norman N
authors.initials: NN
authors.lastname: Iscove
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada.
authors.forename: R Keith
authors.initials: RK
authors.lastname: Humphries
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada.
authors.forename: Connie J
authors.initials: CJ
authors.lastname: Eaves
authors.affiliation: Division of Hematology, Maisonneuve-Rosemont Hospital, Montreal, QC, Canada. Department of Medicine, Faculty of Medicine, Université de Montreal, Montreal, QC, Canada.
authors.forename: Sandra
authors.initials: S
authors.lastname: Cohen
authors.affiliation: Medicinal Chemistry, IRIC, University of Montreal, Montreal, QC, Canada.
authors.forename: Anne
authors.initials: A
authors.lastname: Marinier
authors.affiliation: Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Zandstra
authors.affiliation: 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.
authors.forename: Guy
authors.initials: G
authors.lastname: Sauvageau
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D005312:Fetal Blood / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods; D006410:Hematopoiesis / Q000187:drug effects* / Q000502:physiology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D016867:Immunocompromised Host; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors*; D012038:Regeneration / Q000187:drug effects*; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology
chemical_list: D007211:Indoles; D011743:Pyrimidines; D018336:Receptors, Aryl Hydrocarbon; D054852:Small Molecule Libraries; C000592665:UM171 compound