Pharmacologic Increase in HIF1α Enhances Hematopoietic Stem and Progenitor Homing and Engraftment

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2013 Oct 30

PMID 24167196

Citations 34

Authors

Jennifer M Speth

Jonathan Hoggatt

Pratibha Singh

Louis M Pelus

Affiliations

Soon will be listed here.

Abstract

Hematopoietic stem cell (HSC) transplantation is a lifesaving therapy for a number of immunologic disorders. For effective transplant, HSCs must traffic from the peripheral blood to supportive bone marrow niches. We previously showed that HSC trafficking can be enhanced by ex vivo treatment of hematopoietic grafts with 16-16 dimethyl prostaglandin E2 (dmPGE2). While exploring regulatory molecules involved in dmPGE2 enhancement, we found that transiently increasing the transcription factor hypoxia-inducible factor 1-α (HIF1α) is required for dmPGE2-enhanced CXCR4 upregulation and enhanced migration and homing of stem and progenitor cells and that pharmacologic manipulation of HIF1α is also capable of enhancing homing and engraftment. We also now identify the specific hypoxia response element required for CXCR4 upregulation. These data define a precise mechanism through which ex vivo pulse treatment with dmPGE2 enhances the function of hematopoietic stem and progenitor cells; these data also define a role for hypoxia and HIF1α in enhancement of hematopoietic transplantation.

Citing Articles

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