Small peptide analogs to stromal derived factor-1 enhance chemotactic migration of human and mouse hematopoietic cells

Exp Hematol. 2004 May;32(5):470-5. doi: 10.1016/j.exphem.2004.01.011.

Abstract

Stromal cell-derived factor 1 (SDF-1) is a chemokine that binds to the CXCR4 receptor. Its functions include acting as a chemotactic factor for hematopoietic stem and progenitor cells. We recently reported the synthesis of a small cyclized peptide analog (31 amino acids) of the terminal regions of SDF-1 that had biological function comparable to the native molecule (67 amino acids). In the present study, we investigated the effects of SDF-1 analogs (CTCE0021 and CTCE0214) in the chemotactic migration of peripheral blood hematopoietic cells (lineage-negative and CD34(+) cells). Enhanced chemotaxis of normal and G-CSF-mobilized hematopoietic cells was observed with both SDF-1 analogs in a dose-dependent manner. The increases were statistically significant (p < or = 0.016 by one-way ANOVA) at analog concentrations of 50 to 100 microg/mL. Colony-forming progenitor cells were not affected by exposure to the analogs up to 100 microg/mL. When different doses of the SDF-1 analog CTCE0214 were administered to mice, significant increases in circulating hematopoietic cells (identified by flow cytometry as lineage(low/-), Sca-1(+), and c-kit(+)) were observed after a single injection of 75 microg per animal. The effect was apparent at 4 hours and became significant at 24 hours. These results suggest that SDF-1 analogs can be considered for mobilization of hematopoietic stem cells.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blood Cells
  • Chemokine CXCL12
  • Chemokines, CXC / pharmacology*
  • Chemotaxis / drug effects*
  • Dose-Response Relationship, Drug
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Hematopoietic Stem Cell Mobilization / methods
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Peptides, Cyclic / pharmacology*

Substances

  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • Cxcl12 protein, mouse
  • Peptides, Cyclic
  • Granulocyte Colony-Stimulating Factor