A specific heptapeptide from a phage display peptide library homes to bone marrow and binds to primitive hematopoietic stem cells

Grzegorz S. Nowakowski, Mark S. Dooner, Helen M. Valinski, Alicia M. Mihaliak, Peter J. Quesenberry, Pamela S. Becker

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Phage display peptide libraries have enabled the discovery of peptides that selectively target specific organs. Selection of organ-specific peptides is mediated through binding of peptides displayed on phage coat protein to adhesion molecules expressed within targeted organs. Hematopoietic stem cells selectively home to bone marrow, and certain adhesion receptors critical to this function have been demonstrated. Using a phage display library, we identified a specific peptide that trafficked to murine bone marrow in vivo. We independently isolated exactly the same heptapeptide from the entire library by in vitro biopanning on primitive lineage-depleted, Hoechst 33342 dull/rhodamine 123dull murine bone marrow stem cells and confirmed peptide binding to these cells by immunofluorescence studies. We demonstrated bone marrow-specific homing of the peptide by an in vivo assay in which the animals were injected with the phage displaying peptide sequence, and immunofluorescence analysis of multiple organs was performed. We also showed that the peptide significantly decreased the homing of stem cells to the bone marrow but not to the spleen 3 hours after transplantation using fluorescently labeled Lin-Sca+ hematopoietic cells in an in vivo homing assay. The peptide sequence has a partial (5/7) amino acid sequence homology with a region of CD84. This discovery represents the first application of the phage display methodology to the bone marrow and stem cells and led to the identification of a specific heptapeptide that homes to bone marrow, binds to primitive stem cells, and plays a role in stem cell homing.

Original languageEnglish (US)
Pages (from-to)1030-1038
Number of pages9
JournalStem Cells
Volume22
Issue number6
DOIs
StatePublished - Jan 1 2004

Keywords

  • Bone marrow microenvironment
  • Bone marrow transplant
  • Cell adhesion molecules
  • Engraftment
  • Stem cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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