Pattern of expression of CXCR4 and adhesion molecules by human CD34+ cells from different sources: role in homing efficiency in NOD/SCID mice

Abstract

BACKGROUND AND OBJECTIVES: The role of adhesion molecules (AM) and CXCR4 in the homing of CD34+ cells to NOD/SCID marrow and spleen is not completely elucidated. In this work, we study the differences in the expression of CXCR4 and AM by human CD34+ cells from different sources and their impact on homing ability in NOD/SCID mice. DESIGN AND METHODS: We used flow cytometry to analyze the expression of CXCR4 and AM ( CD49d, CD49e, CD11a, CD58, CD54, CD31, CD62L, CD43 and CD44) on fresh CD34+ cells from bone marrow (BM), mobilized peripheral blood (MPB), positively selected CD34+ cells (PS) and after expansion cultures with two cytokine combinations. Secondly, we studied the homing efficiency of CD34+ cells from each source in 75 irradiated NOD/SCID mice, and finally the pattern of expression of CXCR4 and AMs by retrieved human CD34+ cells that had efficiently homed. RESULTS: The homing efficiency of PS CD34+ cells was significantly lower than that of BM and MPB CD34+ cells. Our results reveal that changes in the expression of CXCR4 and AM are induced by mobilization, PS and in vitro expansion. However none of these changes has definitive impact on the homing efficiency. Human CD34+ cells found in the marrow and spleen of NOD/SCID mice have the same adhesive profile as the injected cells: CXCR4, CD62L and CD11a mainly negative, and CD49d+, indicating that homing is not restricted to positive cells. INTERPRETATION AND CONCLUSIONS: We conclude that changes induced in CXCR4 and AM expression after mobilization, selection and expansion of human CD34+ cells do not cause significant differences in the homing efficiency of these cells. The lower homing efficiency of PS CD34 cells could be explained by the absence of accessory cells.