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 33342dull/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.

Glioblastoma patients have a poor prognosis, even after surgery, radiotherapy, and chemotherapy with temozolomide or 1,3-bis(2-chloroethy)-1-nitrosourea. We developed an in vitro recovery model using neurosphere cultures to analyze the efficacy of chemotherapy treatments, and tested whether glioblastoma neurosphere initiating cells are resistant. Concentrations of chemotherapy drugs that inhibit neurosphere formation are similar to clinically relevant doses. Some lines underwent a transient cell cycle arrest and a robust recovery of neurosphere formation. These results indicate that glioblastoma neurospheres can regrow after treatment with chemotherapy drugs. This neurosphere recovery assay will facilitate studies of chemo-resistant subpopulations and methods to enhance glioblastoma therapy.

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