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Blockade of alpha6-integrin reveals diversity in homing patterns among human, baboon, and murine cells
Halvard Bonig1, Gregory V Priestley, Martin Wohlfahrt
1Department of Medicine Division of Hematology, University of Washington, Seattle, Washington, USA.
Our understanding of the mechanisms by which intravenously transplanted hematopoietic stem/progenitor cells (HSPCs) home to and engraft the bone marrow (BM) remains incomplete, but participation of adhesion molecules has been documented. We here demonstrate that blockade of the alpha6-integrin enhanced BM homing of human and nonhuman primate BM-derived HSPCs by >60% in the xenogeneic transplant model and led to significantly improved engraftment. The effect was limited to BM-derived HSPCs, as granulocyte-colony-stimulating factor mobilized peripheral blood or cord blood HSPCs express little or no alpha6 integrin. By contrast, despite high alpha6 integrin expression, no effect of alpha6 blockade on murine BM-HSPCs homing/engraftment was observed.
Our understanding of the mechanisms by which intravenously transplanted hematopoietic stem/progenitor cells (HSPCs) home to and engraft the bone marrow (BM) remains incomplete, but participation of adhesion molecules has been documented. We here demonstrate that blockade of the alpha6-integrin enhanced BM homing of human and nonhuman primate BM-derived HSPCs by >60% in the xenogeneic transplant model and led to significantly improved engraftment. The effect was limited to BM-derived HSPCs, as granulocyte-colony-stimulating factor mobilized peripheral blood or cord blood HSPCs express little or no alpha6 integrin. By contrast, despite high alpha6 integrin expression, no effect of alpha6 blockade on murine BM-HSPCs homing/engraftment was observed.
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