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A Specific Heptapeptide from a Phage Display Peptide Library Homes to Bone Marrow and Binds to Primitive Hematopoietic Stem Cells

^a Division of Gene Therapy, Department of Medicine, University of Massachusetts Medical School,Worcester, Massachusetts, USA;
^b Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA;
^c Department of Research, Roger Williams Medical Center, Providence, Rhode Island, USA;
^d Dana-Farber Cancer Institute, Bostom, Massachusettes, USA;
^e Division of Hematology, University of Washington, Seattle,Washington, USA

Key Words. Stem cells • Engraftment • Bone marrow transplant • Cell adhesion molecules • Bone marrow microenvironment

Correspondence: Pamela S. Becker, M.D., Ph.D., Division of Hematology, Box 357710, University of Washington, 1959 N.E. Pacific Street, HSB K-136, Seattle,WA 98195, USA. Telephone: 206-616-1589; Fax: 206-543-3560; e-mail: pbecker{at}u.washington.edu

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 123^dull 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.