title: Remote ischemic postconditioning enhances cell retention in the myocardium after intravenous administration of bone marrow mesenchymal stromal cells.
abstract: Efficacy of intravenous administration of mesenchymal stromal cells (MSCs) for myocardial infarction (MI) is limited by low cell retention in the damaged myocardium. Previous studies indicated that remote ischemic conditioning could protect against ischemia-reperfusion-induced injury by release of various cytokines including stromal cell derived factor-1 alpha (SDF-1α). However, whether remote ischemic postconditioning (RIPostC) can also enhance the retention of infused cells in the myocardium by activating MSC homing is unclear. In this study, RIPostC was induced with 4cycles of 5min occlusion and reperfusion of the abdominal aorta in female Sprague-Dawley (SD) rats which underwent ligation of the coronary artery 1week previously. Cytokine levels in serum and myocardium were evaluated by enzyme-linked immunosorbent assay (ELISA) at 1, 6, 24 and 48h after RIPostC. Then, a total of 4×10(6) male MSCs were infused intravenously at 24h after RIPostC. The number of survived cells in the myocardium was evaluated by real-time polymerase chain reaction analysis for Y chromosome and the heart function was evaluated by echocardiography at 1month after cell infusion. Furthermore, 10μg/kg rabbit anti-rat CXCR4 polyclonal antibody was injected intraperitoneally to prove the role of SDF-1α for RIPostC. RIPostC induced an increase in SDF-1α in serum at 1h and enhanced SDF-1α transcription and protein synthesis in the myocardium at 24h after the procedure. 1month after cell transplantation, RIPostC significantly increased MSC myocardial retention by 79.1±12.3% and thereby contributed to enhanced cardiac function in comparison with cell transplantation without RIPostC. Furthermore, blockade with a CXCR4-specific antibody after RIPostC markedly attenuated the enhancement of therapeutic efficacy. We conclude that RIPostC activated SDF-1α expression and enhanced retention of the infused MSCs in the injured myocardium. Priming of the heart with RIPostC might be a novel adjunctive approach for intravenous cell delivery.
authors.affiliation: State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Jiang
authors.forename: Peng
authors.initials: P
authors.lastname: Song
authors.forename: Enshi
authors.initials: E
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Shengshou
authors.initials: S
authors.lastname: Hu
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000097:blood; D003331:Coronary Vessels / Q000503:physiopathology; D005260:Female; D005819:Genetic Markers; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology; D057775:Ischemic Postconditioning; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology; D009203:Myocardial Infarction / Q000097:blood / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051876:Sex-Determining Region Y Protein / Q000235:genetics; D013318:Stroke Volume; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D054377:Chemokine CXCL12; D005819:Genetic Markers; D051876:Sex-Determining Region Y Protein; C497747:Sry protein, rat; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat