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

• Published in: Experimental hematology 2004-05, Vol.32 (5), p.470-475
• Main Authors: Zhong, Ruikun, Law, Ping, Wong, Donald, Merzouk, Ahmed, Salari, Hassan, Ball, Edward D
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/j.exphem.2004.01.011

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 ≤ 0.016 by one-way ANOVA) at analog concentrations of 50 to 100 μg/mL. Colony-forming progenitor cells were not affected by exposure to the analogs up to 100 μg/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 μg 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.