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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Culture Techniques
  • Fetal Blood / cytology
  • Fetal Blood / drug effects*
  • Fetal Blood / physiology
  • Genetic Therapy / methods
  • Hematopoiesis / drug effects*
  • Hematopoiesis / physiology
  • Hematopoietic Stem Cell Transplantation / methods
  • Hematopoietic Stem Cells / drug effects*
  • Hematopoietic Stem Cells / physiology
  • Humans
  • Immunocompromised Host
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Mice
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Receptors, Aryl Hydrocarbon / antagonists & inhibitors*
  • Regeneration / drug effects*
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology

Substances

  • Indoles
  • Pyrimidines
  • Receptors, Aryl Hydrocarbon
  • Small Molecule Libraries
  • UM171 compound