Genetically manipulated progenitor/stem cells restore function to the infarcted heart via the SDF-1α/CXCR4 signaling pathway.

Progenitor/stem cells are a viable option to replace myocytes lost subsequent to myocardial infarction (MI). The stromal cell-derived factor-1α/CXC-chemokine receptor type 4 (SDF-1α/CXCR4) axis plays an important role in numerous biological processes including hematopoiesis, cardiogenesis, vasculogenesis, and neuronal development, as well as endothelial progenitor cell trafficking. The secretion of chemoattractants such as SDF-1α at the site of injury creates an environment facilitating the homing of circulating CXCR4 positive and other stem cells (such as mast/stem cell growth factor receptor kit-positive (c-kit(+)) and c-kit(+)/GATA binding protein 4 positive (GATA4(+)) cells) for organ regeneration and tissue repair. SDF-1α is also secreted by hematopoietic progenitor/stem cells and is involved in the autocrine/paracrine regulation of their development and survival. Hypoxic preconditioning activates SDF-1α/CXCR4 signaling and upregulates several vascular/angiogenic factors that cause mobilization of progenitor cells. The SDF-1α/CXCR4 signaling pathway can thus be effectively exploited for cell-based therapy.