Pharmacologic increase in HIF1α enhances hematopoietic stem and progenitor homing and engraftment

Jennifer M. Speth, Jonathan Hoggatt, Pratibha Singh, Louis Pelus

Research output: Contribution to journalArticle

32 Citations (Scopus)

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 pros-taglandin 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.

Original languageEnglish
Pages (from-to)203-207
Number of pages5
JournalBlood
Volume123
Issue number2
DOIs
StatePublished - Jan 9 2014

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Hypoxia-Inducible Factor 1
Hematopoietic Stem Cells
Stem cells
Up-Regulation
Stem Cells
Transplants
Hematopoietic Stem Cell Transplantation
Response Elements
Grafts
Bone
Blood
Transcription Factors
Therapeutics
Transplantation
Bone Marrow
Molecules
Hypoxia

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Pharmacologic increase in HIF1α enhances hematopoietic stem and progenitor homing and engraftment. / Speth, Jennifer M.; Hoggatt, Jonathan; Singh, Pratibha; Pelus, Louis.

In: Blood, Vol. 123, No. 2, 09.01.2014, p. 203-207.

Research output: Contribution to journalArticle

Speth, Jennifer M. ; Hoggatt, Jonathan ; Singh, Pratibha ; Pelus, Louis. / Pharmacologic increase in HIF1α enhances hematopoietic stem and progenitor homing and engraftment. In: Blood. 2014 ; Vol. 123, No. 2. pp. 203-207.
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