Improvement of Cardiac Stem Cell-Sheet Therapy for Chronic Ischemic Injury by Adding Endothelial Progenitor Cell Transplantation: Analysis of Layer-Specific Regional Cardiac Function
Author: Sokichi Kamata, Shigeru Miyagawa, Satsuki Fukushima, Satoshi Nakatani, Atsuhiko Kawamoto, Atsuhiro Saito, Akima Harada, Tatsuya Shimizu, Takashi Daimon, Teruo Okano, Takayuki Asahara, Yoshiki Sawa.
Source: Cell Transplantation
Publisher: Cognizant Communication Corporation
Abstract:BACKGROUND: The transplantation of cardiac stem cell sheets (CSC sheets) is apromising therapeutic strategy for ischemic cardiomyopathy, although potential ischemia inthe transplanted area remains a problem. Injected endothelial progenitor cells (EPCs) canreportedly induce angiogenesis in the injected area. We hypothesized that concomitant CSCsheet transplantation and EPC injection might show better therapeutic effects for chronicischemic injury model than the transplantation of CSC sheets alone.METHODS: Scaffold-free CSC-sheets were generated from human c-kit-positive heartderivedcells. A porcine chronic ischemic injury model was generated by placing an ameroidconstrictor around the left coronary artery for 4 weeks. The animals then underwent a shamoperation, epicardial transplantation of CSC sheet over the ischemic area, intramyocardialinjection of EPCs into the ischemic and peri-ischemic area, or CSC-sheet transplantation plusEPC injection. The efficacy of each treatment was then assessed for 2 months.RESULTS: Speckle-tracking echocardiography was used to dissect the layer-specificregional systolic function by measuring the radial strain (RS). The epicardial RS in theischemic area was similarly greater after treatment with the CSC-derived cell-sheets alone(19±5%) or in combination with EPC injection (20±5%) compared with the EPC only(9±4%) or sham (7±1%) treatment. The endocardial RS in the ischemic area was greatestafter the combined treatment (14±1%), followed by EPC only (12±1%), compared to theCSC only (11±1%) and sham (9±1%) treatments. Consistently, either epicardial CSC-sheetimplantation or intramyocardial EPC injection yielded increased capillary number andreduced cardiac fibrosis in the ischemic epicardium or endocardium, respectively.Concomitant EPC injection induced the migration of transplanted CSCs into the hostCopyright © 2013 Cognizant Communication CorporationCT-0968 Cell Transplantation Epub; provisional acceptance 02/27/2013 3myocardium, leading to further neovascularization and reduced fibrosis in the ischemicendocardium, compared to the CSC-sole therapy.CONCLUSION: Transplantation of CSC-sheets induced significant functional recovery ofthe ischemic epicardium, and concomitant EPC transplantation elicited transmuralimprovement in chronic ischemic injury.
Appeared or available online: April 3, 2013