Enhancing the Migration Ability of Mesenchymal Stromal Cells by Targeting the SDF-1/CXCR4 Axis
Figure 1
Mechanisms of MSC transendothelial migration towards injured tissue. Mesenchymal stromal cells (MSCs) express the α 4β 1 integrin very late antigen (VLA)-4, and endothelial cells express the corresponding ligand, vascular cell adhesion molecule (VCAM)-1. The onset of inflammation in injured tissue causes the release of cytokines which upregulate VCAM-1 and activates VLA-4, leading to initial arrest of MSC on the endothelium surface. MSCs also express a variety of homing receptors including CXCR4, CD44, CCR1, and c-Met, and their corresponding ligands, namely SDF-1, hyaluronic acid, M1P-1(alpha), and HGF, respectively, are upregulated at the site of tissue injury and/or hypoxia. These ligand-receptor interactions, as well as chemotactic bioactive lipids, modulate cell-cell contact between MSCs and endothelia cells. In addition, complement proteins that are stimulated by inflammation such as C1q, C3a, and C5a also chemoattract MSCs. Moreover, MSCs express the extracellular matrix-degrading enzymes, matrix metalloproteinase-(MMP-) 2 and membrane type (MT)1-MMP that play a role in their extravasation.
