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.
Department of Pathology and Laboratory Medicine, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
Yigang
Y
Wang
Kristin
K
Luther
D000818:Animals; D054377:Chemokine CXCL12 / Q000378:metabolism*; D005818:Genetic Engineering / Q000379:methods*; D006801:Humans; D009203:Myocardial Infarction / Q000503:physiopathology* / Q000628:therapy*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism*
D054377:Chemokine CXCL12; D019718:Receptors, CXCR4