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

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 serumfree 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, decHOXtreated 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. [ABSTRACT FROM AUTHOR]