Cord Blood Expansion. Pyrimidoindole Derivatives Are Agonists of Human Hematopoietic Stem Cell Self-renewal

Overview

Journal Science

Specialty Science

Date 2014 Sep 20

PMID 25237102

Citations 290

Authors

Iman Fares

Jalila Chagraoui

Yves Gareau

Stephane Gingras

Rejean Ruel

Nadine Mayotte

Elizabeth Csaszar

David J H F Knapp

Paul Miller

Mor Ngom

Suzan Imren

Denis-Claude Roy

Kori L Watts

Hans-Peter Kiem

Robert Herrington

Norman N Iscove

R Keith Humphries

Connie J Eaves

Sandra Cohen

Anne Marinier

Peter W Zandstra

Guy Sauvageau

Affiliations

Soon will be listed here.

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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