AIMS: The objective of this study was to investigate whether vascular endothelial growth factor (VEGF) secreted by mesenchymal stem cells (MSC) improves myocardial survival and the engraftment of implanted MSC in infarcted hearts and promotes recruitment of stem cells through paracrine release of myocardial stromal cell-derived factor-1α (SDF-1α). METHODS AND RESULTS: VEGF-expressing MSC ((VEGF)MSC)-conditioned medium enhanced SDF-1α expression in heart slices and H9C2 cardiomyoblast cells via VEGF and the vascular endothelial growth factor receptor (VEGFR). The (VEGF)MSC-conditioned medium markedly promoted cardiac stem cell (CSC) migration at least in part via the SDF-1α/CXCR4 pathway and involved binding to VEGFR-1 and VEGFR-3. In vivo, (VEGF)MSC-stimulated SDF-1α expression in infarcted hearts resulted in massive mobilization and homing of bone marrow stem cells and CSC. Moreover, VEGF-induced SDF-1α guided the exogenously introduced CSC in the atrioventricular groove to migrate to the infarcted area, leading to a reduction in infarct size. Functional studies showed that (VEGF)MSC transplantation stimulated extensive angiomyogenesis in infarcted hearts as indicated by the expression of cardiac troponin T, CD31, and von Willebrand factor and improved the left ventricular performance, whereas blockade of SDF-1α or its receptor by RNAi or antagonist significantly diminished the beneficial effects of (VEGF)MSC. CONCLUSION: Exogenously expressed VEGF promotes myocardial repair at least in part through SDF-1α/CXCR4-mediated recruitment of CSC.
AIMS: The objective of this study was to investigate whether vascular endothelial growth factor (VEGF) secreted by mesenchymal stem cells (MSC) improves myocardial survival and the engraftment of implanted MSC in infarcted hearts and promotes recruitment of stem cells through paracrine release of myocardial stromal cell-derived factor-1α (SDF-1α). METHODS AND RESULTS:VEGF-expressing MSC ((VEGF)MSC)-conditioned medium enhanced SDF-1α expression in heart slices and H9C2 cardiomyoblast cells via VEGF and the vascular endothelial growth factor receptor (VEGFR). The (VEGF)MSC-conditioned medium markedly promoted cardiac stem cell (CSC) migration at least in part via the SDF-1α/CXCR4 pathway and involved binding to VEGFR-1 and VEGFR-3. In vivo, (VEGF)MSC-stimulated SDF-1α expression in infarcted hearts resulted in massive mobilization and homing of bone marrow stem cells and CSC. Moreover, VEGF-induced SDF-1α guided the exogenously introduced CSC in the atrioventricular groove to migrate to the infarcted area, leading to a reduction in infarct size. Functional studies showed that (VEGF)MSC transplantation stimulated extensive angiomyogenesis in infarcted hearts as indicated by the expression of cardiac troponin T, CD31, and von Willebrand factor and improved the left ventricular performance, whereas blockade of SDF-1α or its receptor by RNAi or antagonist significantly diminished the beneficial effects of (VEGF)MSC. CONCLUSION: Exogenously expressed VEGF promotes myocardial repair at least in part through SDF-1α/CXCR4-mediated recruitment of CSC.
Authors: Massimiliano Gnecchi; Huamei He; Olin D Liang; Luis G Melo; Fulvio Morello; Hui Mu; Nicolas Noiseux; Lunan Zhang; Richard E Pratt; Joanne S Ingwall; Victor J Dzau Journal: Nat Med Date: 2005-04 Impact factor: 53.440
Authors: Sang Yup Lim; Yong Sook Kim; Youngkeun Ahn; Myung Ho Jeong; Moon Hwa Hong; Soo Yeon Joo; Kwang Il Nam; Jeong Gwan Cho; Peter M Kang; Jong Chun Park Journal: Cardiovasc Res Date: 2006-03-06 Impact factor: 10.787
Authors: Carmen Urbich; Alexandra Aicher; Christopher Heeschen; Elisabeth Dernbach; Wolf K Hofmann; Andreas M Zeiher; Stefanie Dimmeler Journal: J Mol Cell Cardiol Date: 2005-09-29 Impact factor: 5.000
Authors: Guilherme V Silva; Silvio Litovsky; Joao A R Assad; Andre L S Sousa; Bradley J Martin; Deborah Vela; Stephanie C Coulter; Jing Lin; Judy Ober; William K Vaughn; Rodrigo V C Branco; Edie M Oliveira; Rumin He; Yong-Jian Geng; James T Willerson; Emerson C Perin Journal: Circulation Date: 2005-01-10 Impact factor: 29.690
Authors: Massimiliano Gnecchi; Huamei He; Nicolas Noiseux; Olin D Liang; Lunan Zhang; Fulvio Morello; Hui Mu; Luis G Melo; Richard E Pratt; Joanne S Ingwall; Victor J Dzau Journal: FASEB J Date: 2006-04 Impact factor: 5.191
Authors: Kristine C Rustad; Victor W Wong; Michael Sorkin; Jason P Glotzbach; Melanie R Major; Jayakumar Rajadas; Michael T Longaker; Geoffrey C Gurtner Journal: Biomaterials Date: 2011-10-02 Impact factor: 12.479
Authors: D Zhao; C Pan; J Sun; C Gilbert; K Drews-Elger; D J Azzam; M Picon-Ruiz; M Kim; W Ullmer; D El-Ashry; C J Creighton; J M Slingerland Journal: Oncogene Date: 2014-08-25 Impact factor: 9.867
Authors: Daryl O Nelson; Pratik A Lalit; Mitch Biermann; Yogananda S Markandeya; Deborah L Capes; Luke Addesso; Gina Patel; Tianxiao Han; Manorama C John; Patricia A Powers; Karen M Downs; Timothy J Kamp; Gary E Lyons Journal: Stem Cells Date: 2016-09-13 Impact factor: 6.277