Title

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

UMMS Affiliation

Department of Medicine, Division of Gene Therapy; Cancer Center

Date

11-13-2004

Document Type

Article

Subjects

Animals; Blotting, Western; Bone Marrow Cells; Cell Adhesion; Cell Lineage; Cell Separation; Chromatography; Databases as Topic; Flow Cytometry; Hematopoietic Stem Cells; Mice; Mice, Inbred BALB C; Microscopy, Fluorescence; Models, Biological; *Peptide Library; Peptides; Protein Binding

Disciplines

Life Sciences | Medicine and Health Sciences

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 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.

Rights and Permissions

Citation: Stem Cells. 2004;22(6):1030-8. Link to article on publisher's site

DOI of Published Version

10.1634/stemcells.22-6-1030

Related Resources

Link to Article in PubMed

Journal Title

Stem cells (Dayton, Ohio)

PubMed ID

15536193