Stromal cell derived factor-1/CXCL12, CXCR4 and CD26 in the mobilization and homing of hematopoietic stem and progenitor cells

Hal Broxmeyer, K. W. Christopherson

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Hematopoietic Stem (HSC) and Progenitor (HPC) cells are rare and give rise to all blood forming cells. In many malignant and non-malignant disorders, a transplant of HSC/HPC is the only curative regiment available for these disorders. Transplants of HSC/HPC are done through intravenous injection of donor cells into conditioned recipients where the cells home to and engraft in the bone marrow. The majority of HSC/HPC transplants are currently performed with these cells after they are mobilized from the marrow to circulating blood where they are then collected for transplantation. Chemokines are recognized for their chemoattractant/chemotactic capabilities of many different cell types. Stromal Cell Derived Factor-1 (SDF-1/CXCL12) and its receptor, CXCR4 have been implicated by us and others in the migration in vitro and in vivo of HSC/HPC. This paper reviews the role and practical implications of the SDF-1/CXCL12-CXCR4 axis in the homing, engraftment and mobilization of HSC, and the modulation of these events by the cell surface component CD26, which manifests Dipeptidylpeptidase IV (DPPIV) activity that truncates SDF-1/CXCL12 and changes its activity, and by AMD3100, a specific antagonist of SDF-1/CXCL12 binding to CXCR4. Inhibition or deletion of CD26 has been used to enhance the homing and engrafting capabilities of murine HSC, while AMD3100 has been used to induce mobilization of murine and human HSC and HPC, and to enhance this mobilization induced by Granulocyte-Colony Stimulating Factor. Further efforts in understanding the SDF-1/CXCL12-CXCR4 axis, and CD26 and their mechanisms of actions and modulation should yield information of clinical relevance and utility.

Original languageEnglish
Pages (from-to)303-311
Number of pages9
JournalCurrent Medicinal Chemistry: Anti-Inflammatory and Anti-Allergy Agents
Volume3
Issue number4
DOIs
StatePublished - Dec 2004

Fingerprint

Chemokine CXCL12
Hematopoietic Stem Cells
Transplants
Bone Marrow
CXCR4 Receptors
Chemotactic Factors
Granulocyte Colony-Stimulating Factor
Cellular Structures
Chemokines
Intravenous Injections
Blood Cells
Stem Cells
Transplantation
JM 3100

Keywords

  • CD26
  • Chemokines
  • Chemotaxis
  • CXCL12
  • CXCR4
  • Cytokines
  • Granulocyte colony stimulating factor
  • Homing
  • Mobilization
  • Stem cells
  • Transplantation

ASJC Scopus subject areas

  • Pharmacology
  • Immunology
  • Immunology and Allergy

Cite this

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title = "Stromal cell derived factor-1/CXCL12, CXCR4 and CD26 in the mobilization and homing of hematopoietic stem and progenitor cells",
abstract = "Hematopoietic Stem (HSC) and Progenitor (HPC) cells are rare and give rise to all blood forming cells. In many malignant and non-malignant disorders, a transplant of HSC/HPC is the only curative regiment available for these disorders. Transplants of HSC/HPC are done through intravenous injection of donor cells into conditioned recipients where the cells home to and engraft in the bone marrow. The majority of HSC/HPC transplants are currently performed with these cells after they are mobilized from the marrow to circulating blood where they are then collected for transplantation. Chemokines are recognized for their chemoattractant/chemotactic capabilities of many different cell types. Stromal Cell Derived Factor-1 (SDF-1/CXCL12) and its receptor, CXCR4 have been implicated by us and others in the migration in vitro and in vivo of HSC/HPC. This paper reviews the role and practical implications of the SDF-1/CXCL12-CXCR4 axis in the homing, engraftment and mobilization of HSC, and the modulation of these events by the cell surface component CD26, which manifests Dipeptidylpeptidase IV (DPPIV) activity that truncates SDF-1/CXCL12 and changes its activity, and by AMD3100, a specific antagonist of SDF-1/CXCL12 binding to CXCR4. Inhibition or deletion of CD26 has been used to enhance the homing and engrafting capabilities of murine HSC, while AMD3100 has been used to induce mobilization of murine and human HSC and HPC, and to enhance this mobilization induced by Granulocyte-Colony Stimulating Factor. Further efforts in understanding the SDF-1/CXCL12-CXCR4 axis, and CD26 and their mechanisms of actions and modulation should yield information of clinical relevance and utility.",
keywords = "CD26, Chemokines, Chemotaxis, CXCL12, CXCR4, Cytokines, Granulocyte colony stimulating factor, Homing, Mobilization, Stem cells, Transplantation",
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year = "2004",
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T1 - Stromal cell derived factor-1/CXCL12, CXCR4 and CD26 in the mobilization and homing of hematopoietic stem and progenitor cells

AU - Broxmeyer, Hal

AU - Christopherson, K. W.

PY - 2004/12

Y1 - 2004/12

N2 - Hematopoietic Stem (HSC) and Progenitor (HPC) cells are rare and give rise to all blood forming cells. In many malignant and non-malignant disorders, a transplant of HSC/HPC is the only curative regiment available for these disorders. Transplants of HSC/HPC are done through intravenous injection of donor cells into conditioned recipients where the cells home to and engraft in the bone marrow. The majority of HSC/HPC transplants are currently performed with these cells after they are mobilized from the marrow to circulating blood where they are then collected for transplantation. Chemokines are recognized for their chemoattractant/chemotactic capabilities of many different cell types. Stromal Cell Derived Factor-1 (SDF-1/CXCL12) and its receptor, CXCR4 have been implicated by us and others in the migration in vitro and in vivo of HSC/HPC. This paper reviews the role and practical implications of the SDF-1/CXCL12-CXCR4 axis in the homing, engraftment and mobilization of HSC, and the modulation of these events by the cell surface component CD26, which manifests Dipeptidylpeptidase IV (DPPIV) activity that truncates SDF-1/CXCL12 and changes its activity, and by AMD3100, a specific antagonist of SDF-1/CXCL12 binding to CXCR4. Inhibition or deletion of CD26 has been used to enhance the homing and engrafting capabilities of murine HSC, while AMD3100 has been used to induce mobilization of murine and human HSC and HPC, and to enhance this mobilization induced by Granulocyte-Colony Stimulating Factor. Further efforts in understanding the SDF-1/CXCL12-CXCR4 axis, and CD26 and their mechanisms of actions and modulation should yield information of clinical relevance and utility.

AB - Hematopoietic Stem (HSC) and Progenitor (HPC) cells are rare and give rise to all blood forming cells. In many malignant and non-malignant disorders, a transplant of HSC/HPC is the only curative regiment available for these disorders. Transplants of HSC/HPC are done through intravenous injection of donor cells into conditioned recipients where the cells home to and engraft in the bone marrow. The majority of HSC/HPC transplants are currently performed with these cells after they are mobilized from the marrow to circulating blood where they are then collected for transplantation. Chemokines are recognized for their chemoattractant/chemotactic capabilities of many different cell types. Stromal Cell Derived Factor-1 (SDF-1/CXCL12) and its receptor, CXCR4 have been implicated by us and others in the migration in vitro and in vivo of HSC/HPC. This paper reviews the role and practical implications of the SDF-1/CXCL12-CXCR4 axis in the homing, engraftment and mobilization of HSC, and the modulation of these events by the cell surface component CD26, which manifests Dipeptidylpeptidase IV (DPPIV) activity that truncates SDF-1/CXCL12 and changes its activity, and by AMD3100, a specific antagonist of SDF-1/CXCL12 binding to CXCR4. Inhibition or deletion of CD26 has been used to enhance the homing and engrafting capabilities of murine HSC, while AMD3100 has been used to induce mobilization of murine and human HSC and HPC, and to enhance this mobilization induced by Granulocyte-Colony Stimulating Factor. Further efforts in understanding the SDF-1/CXCL12-CXCR4 axis, and CD26 and their mechanisms of actions and modulation should yield information of clinical relevance and utility.

KW - CD26

KW - Chemokines

KW - Chemotaxis

KW - CXCL12

KW - CXCR4

KW - Cytokines

KW - Granulocyte colony stimulating factor

KW - Homing

KW - Mobilization

KW - Stem cells

KW - Transplantation

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U2 - 10.2174/1568014043355249

DO - 10.2174/1568014043355249

M3 - Article

VL - 3

SP - 303

EP - 311

JO - Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry

JF - Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry

SN - 1871-5230

IS - 4

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