Stem cell rolling interactions, SDF-1 interactions, and migrating stem cells.

(A) Stem cell rolling interactions on constitutively expressed endothelial E and P selectins. Following rolling, CXCR4⁺stem cells (blue cells) are activated by SDF-1, which is secreted from bone marrow endothelial cells and triggers LFA-1/ICAM-1 and VLA-4/VCAM-1 interactions to support firm adhesion to endothelial cells. (B) Cells that do not express sufficient levels of CXCR4 (purple) will detach from the endothelial layer and return to the blood stream. (C) The arrested human CXCR4⁺ stem cells, in response to SDF-1, will extravasate and migrate through the underlying basal lamina ECM using VLA-4 and VLA-5 integrin receptors to FN. (D) Migrating stem cells will eventually reach the “stem cell niches,” which consist of stromal cells that present the proper set of adhesion molecules (eg, VCAM-1 and FN), SDF-1, and growth stimulatory factors.