Overexpression of Stromal Cell–derived Factor-1 Enhances Endothelium-supported Transmigration, Maintenance, and Proliferation of Hematopoietic Progenitor Cells

Abstract

To clarify the direct effects of aberrant overexpression of stromal cell-derived factor-1 (SDF-1) by the human endothelium on circulating progenitor cells, we overexpressed the SDF-1 gene in human umbilical vein endothelial cells using an adenoviral vector (HUVEC/AdeSDF-1) and examined the endothelium-supported trafficking and growth of hematopoietic progenitor cells (HPCs) in mobilized peripheral blood (mPB). In culture, the HUVEC/AdeSDF-1 monolayers induced the migration of mPB CD34(+) cells underneath the endothelium within a few hours, whereas HUVEC monolayers that expressed the LacZ gene (HUVEC/AdeLacZ) did not have this effect. In the Transwell system, the HUVEC/AdeSDF-1 cells supported a higher level of spontaneous transmigration of mPB CD34(+) cells than did the HUVEC/AdeLacZ cells. The co-culturing of mPB CD34(+) cells with HUVEC/ AdeSDF-1 cells led to a greater expansion of CD45(+) cells and colony-forming cells and reduced cellular apoptosis. Furthermore, the co-culturing of mPB CD34(+) cells with HUVEC/AdeSDF-1 cells led to the formation of numerous cobblestone-like areas, whereas co-cultures of mPB CD34(+) cells and HUVEC/AdeLacZ supported only a few cobblestone-like areas. These results indicate that SDF- 1 produced by endothelial cells plays an important role not only in the transmigration but also in the growth of HPCs that are in contact with endothelial cells. Our findings suggest that the enhanced expression and production of SDF-1 in the endothelium are essential steps for stem cell or progenitor cell recruitment to specific tissues and for the maintenance of these cells in situ.