Treatment of circulating CD34+ cells with SDF-1α or anti-CXCR4 antibody enhances migration and NOD/SCID repopulating potential

P. Artur Plett, Stacy M. Frankovitz, Frances M. Wolber, Rafat Abonour, Christie Orschell

Research output: Contribution to journalArticle

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Abstract

Objective. Stromal cell-derived factor-1α (SDF-1α) has been implicated in homing and engraftment of primitive hematopoietic progenitor cells (HPC) in studies demonstrating reduced NOD/SCID repopulating potential of HPC exposed to supra-physiologic concentrations of SDF-1α or anti-CXCR4. Outcome of CXCR4 signaling in some cells has been shown to be dependent on the concentration of SDF-1α. We aimed to determine whether similar concentration-dependent responses to CXCR4 signaling are present in CD34+cells. Materials and Methods. Human peripheral blood (PB), mobilized PB (MPB), or bone marrow (BM) CD34+ cells were incubated for 30 minutes with different concentrations of SDF-1α or anti-CXCR4, washed, then assessed for in vitro hematopoietic potential, migration, and NOD/SCID repopulating potential. Results. Exposure of MPB or PB CD34+ cells to 100 ng/mL SDF-1α increased tyrosine phosphorylation without subsequent proliferation or apoptosis. Spontaneous and SDF-1α-directed migration also increased in pretreated cells, despite previous exposure to SDF-1α. Cells exposed to 1 μg anti-CXCR4/106 cells displayed similar increases in activation and migration as cells exposed to SDF-1α, demonstrating the ability of anti-CXCR4 to activate the CXCR4 receptor. Interestingly, chimerism in NOD/SCID mice transplanted with MPB CD34+ cells pretreated with SDF-1α or anti-CXCR4 was increased, while exposure of these cells to 10- to 100-fold higher concentrations of these proteins inhibited in vitro migration and NOD/SCID repopulating potential. Migration and NOD/SCID repopulating potential of BM CD34+ cells remained unchanged after treatment with either protein. Conclusions. These results illustrate the ability of SDF-1α and anti-CXCR4 to augment repopulating potential of CD34+ cells, and suggest that HPC function can be favorably modulated through specific CXCR4 signaling.

Original languageEnglish
Pages (from-to)1061-1069
Number of pages9
JournalExperimental Hematology
Volume30
Issue number9
DOIs
StatePublished - Sep 2002

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Chemokine CXCL12
Anti-Idiotypic Antibodies
Hematopoietic Stem Cells
Bone Marrow Cells
CXCR4 Receptors
Inbred NOD Mouse
Chimerism
SCID Mice
Cell Movement
Tyrosine
Blood Cells
Proteins
Phosphorylation
Apoptosis

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

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Treatment of circulating CD34+ cells with SDF-1α or anti-CXCR4 antibody enhances migration and NOD/SCID repopulating potential. / Plett, P. Artur; Frankovitz, Stacy M.; Wolber, Frances M.; Abonour, Rafat; Orschell, Christie.

In: Experimental Hematology, Vol. 30, No. 9, 09.2002, p. 1061-1069.

Research output: Contribution to journalArticle

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abstract = "Objective. Stromal cell-derived factor-1α (SDF-1α) has been implicated in homing and engraftment of primitive hematopoietic progenitor cells (HPC) in studies demonstrating reduced NOD/SCID repopulating potential of HPC exposed to supra-physiologic concentrations of SDF-1α or anti-CXCR4. Outcome of CXCR4 signaling in some cells has been shown to be dependent on the concentration of SDF-1α. We aimed to determine whether similar concentration-dependent responses to CXCR4 signaling are present in CD34+cells. Materials and Methods. Human peripheral blood (PB), mobilized PB (MPB), or bone marrow (BM) CD34+ cells were incubated for 30 minutes with different concentrations of SDF-1α or anti-CXCR4, washed, then assessed for in vitro hematopoietic potential, migration, and NOD/SCID repopulating potential. Results. Exposure of MPB or PB CD34+ cells to 100 ng/mL SDF-1α increased tyrosine phosphorylation without subsequent proliferation or apoptosis. Spontaneous and SDF-1α-directed migration also increased in pretreated cells, despite previous exposure to SDF-1α. Cells exposed to 1 μg anti-CXCR4/106 cells displayed similar increases in activation and migration as cells exposed to SDF-1α, demonstrating the ability of anti-CXCR4 to activate the CXCR4 receptor. Interestingly, chimerism in NOD/SCID mice transplanted with MPB CD34+ cells pretreated with SDF-1α or anti-CXCR4 was increased, while exposure of these cells to 10- to 100-fold higher concentrations of these proteins inhibited in vitro migration and NOD/SCID repopulating potential. Migration and NOD/SCID repopulating potential of BM CD34+ cells remained unchanged after treatment with either protein. Conclusions. These results illustrate the ability of SDF-1α and anti-CXCR4 to augment repopulating potential of CD34+ cells, and suggest that HPC function can be favorably modulated through specific CXCR4 signaling.",
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T1 - Treatment of circulating CD34+ cells with SDF-1α or anti-CXCR4 antibody enhances migration and NOD/SCID repopulating potential

AU - Plett, P. Artur

AU - Frankovitz, Stacy M.

AU - Wolber, Frances M.

AU - Abonour, Rafat

AU - Orschell, Christie

PY - 2002/9

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N2 - Objective. Stromal cell-derived factor-1α (SDF-1α) has been implicated in homing and engraftment of primitive hematopoietic progenitor cells (HPC) in studies demonstrating reduced NOD/SCID repopulating potential of HPC exposed to supra-physiologic concentrations of SDF-1α or anti-CXCR4. Outcome of CXCR4 signaling in some cells has been shown to be dependent on the concentration of SDF-1α. We aimed to determine whether similar concentration-dependent responses to CXCR4 signaling are present in CD34+cells. Materials and Methods. Human peripheral blood (PB), mobilized PB (MPB), or bone marrow (BM) CD34+ cells were incubated for 30 minutes with different concentrations of SDF-1α or anti-CXCR4, washed, then assessed for in vitro hematopoietic potential, migration, and NOD/SCID repopulating potential. Results. Exposure of MPB or PB CD34+ cells to 100 ng/mL SDF-1α increased tyrosine phosphorylation without subsequent proliferation or apoptosis. Spontaneous and SDF-1α-directed migration also increased in pretreated cells, despite previous exposure to SDF-1α. Cells exposed to 1 μg anti-CXCR4/106 cells displayed similar increases in activation and migration as cells exposed to SDF-1α, demonstrating the ability of anti-CXCR4 to activate the CXCR4 receptor. Interestingly, chimerism in NOD/SCID mice transplanted with MPB CD34+ cells pretreated with SDF-1α or anti-CXCR4 was increased, while exposure of these cells to 10- to 100-fold higher concentrations of these proteins inhibited in vitro migration and NOD/SCID repopulating potential. Migration and NOD/SCID repopulating potential of BM CD34+ cells remained unchanged after treatment with either protein. Conclusions. These results illustrate the ability of SDF-1α and anti-CXCR4 to augment repopulating potential of CD34+ cells, and suggest that HPC function can be favorably modulated through specific CXCR4 signaling.

AB - Objective. Stromal cell-derived factor-1α (SDF-1α) has been implicated in homing and engraftment of primitive hematopoietic progenitor cells (HPC) in studies demonstrating reduced NOD/SCID repopulating potential of HPC exposed to supra-physiologic concentrations of SDF-1α or anti-CXCR4. Outcome of CXCR4 signaling in some cells has been shown to be dependent on the concentration of SDF-1α. We aimed to determine whether similar concentration-dependent responses to CXCR4 signaling are present in CD34+cells. Materials and Methods. Human peripheral blood (PB), mobilized PB (MPB), or bone marrow (BM) CD34+ cells were incubated for 30 minutes with different concentrations of SDF-1α or anti-CXCR4, washed, then assessed for in vitro hematopoietic potential, migration, and NOD/SCID repopulating potential. Results. Exposure of MPB or PB CD34+ cells to 100 ng/mL SDF-1α increased tyrosine phosphorylation without subsequent proliferation or apoptosis. Spontaneous and SDF-1α-directed migration also increased in pretreated cells, despite previous exposure to SDF-1α. Cells exposed to 1 μg anti-CXCR4/106 cells displayed similar increases in activation and migration as cells exposed to SDF-1α, demonstrating the ability of anti-CXCR4 to activate the CXCR4 receptor. Interestingly, chimerism in NOD/SCID mice transplanted with MPB CD34+ cells pretreated with SDF-1α or anti-CXCR4 was increased, while exposure of these cells to 10- to 100-fold higher concentrations of these proteins inhibited in vitro migration and NOD/SCID repopulating potential. Migration and NOD/SCID repopulating potential of BM CD34+ cells remained unchanged after treatment with either protein. Conclusions. These results illustrate the ability of SDF-1α and anti-CXCR4 to augment repopulating potential of CD34+ cells, and suggest that HPC function can be favorably modulated through specific CXCR4 signaling.

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