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TRANSLATIONAL AND CLINICAL RESEARCH

HOX Decoy Peptide Enhances the Ex Vivo Expansion of Human Umbilical Cord Blood CD34⁺ Hematopoietic Stem Cells/Hematopoietic Progenitor Cells

^aDepartment of Regenerative Medicine, Institute of Biomedical Research and Innovation, Kobe, Japan;
^bDepartment of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan;
^cDepartment of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan

Key Words. Ex vivo expansion • Hematopoietic stem/progenitor cells • HOX • Peptide mimetics

Correspondence: Hirokazu Tanaka, M.D., Ph.D., Department of Hematology and Oncology, Osaka University Graduate School of Medicine, C9, 2-2, Yamada-oka, Suita, Osaka 565-0871, Japan. Telephone: 81-6-6879-3871; Fax: 81-6-6879-3879; e-mail: htanaka{at}fbri.org

Received November 6, 2005; accepted for publication July 14, 2006.


HOX transcription factors play important roles in the self-renewal of hematopoietic cells. HOX proteins interact with the non-HOX homeobox protein PBX1 to regulate, both positively and negatively, the expression of target genes. In this study, we synthesized a decoy peptide containing the YPWM motif from HOX proteins (decoy HOX [decHOX]), which was predicted to act as a HOX mimetic, and analyzed its effects on self-renewal of human cord blood CD34⁺ cells. We were able to deliver decHOX into approximately 70% of CD34⁺ cells. By examining the expression of HOX target genes c-myc and p21^waf1/cip1, we confirmed that decHOX enhanced HOX functions. After 7 days of culture in serum-free medium containing a cytokine cocktail, cultures treated with decHOX had approximately twofold-increased numbers of CD34⁺ cells and primitive multipotent progenitor cells compared with control cells. Furthermore, decHOX-treated cells reconstituted hematopoiesis in nonobese diabetic/severe combined immunodeficiency mice more rapidly and more effectively (more than twofold greater efficiency, as determined by a limiting dilution method) than control cells. decHOX-treated cells were also able to repopulate secondary recipients. Together, these results indicate that in combination with growth factors and/or other approaches, decHOX might be a useful new tool for the ex vivo expansion of hematopoietic stem/progenitor cells.