Direct implantation versus platelet-rich fibrin-embedded adipose-derived mesenchymal stem cells in treating rat acute myocardial infarction |
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Authors: | Cheuk-Kwan Sun Yen-Yi Zhen Steve Leu Tzu-Hsien Tsai Li-Teh Chang Jiunn-Jye Sheu Yung-Lung Chen Sarah Chua Han-Tan Chai Hung-I Lu Hsueh-Wen Chang Fan-Yen Lee Hon-Kan Yip |
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Institution: | 1. Department of Emergency Medicine, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan;2. Division of Cardiology, Department of Internal Medicine, Taiwan;3. Center for Translational Research in Biomedical Sciences, Taiwan;4. Basic Science, Nursing Department, Meiho Institute of Technology, Pingtung, Taiwan;5. Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan;6. Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan |
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Abstract: | BackgroundThis study tested whether adipose-derived mesenchymal stem cells (ADMSC) embedded in platelet-rich fibrin (PRF) scaffold is superior to direct ADMSC implantation in improving left ventricular (LV) performance and reducing LV remodeling in a rat acute myocardial infarction (AMI) model of left anterior descending coronary artery (LAD) ligation.MethodsTwenty-eight male adult Sprague Dawley rats equally divided into group 1 sham control], group 2 (AMI only), group 3 (AMI + direct ADMSC implantation), and group 4 (AMI + PRF-embedded autologous ADMSC) were sacrificed on day 42 after AMI.ResultsLV systolic and diastolic dimensions and volumes, and infarct/fibrotic areas were highest in group 2, lowest in group 1 and significantly higher in group 3 than in group 4, whereas LV performance and LV fractional shortening exhibited a reversed pattern (p < 0.005). Protein expressions of inflammation (oxidative stress, IL-1β, MMP-9), apoptosis (mitochondrial Bax, cleaved PARP), fibrosis (Smad3, TGF-β), and pressure-overload biomarkers (BNP, MHC-β) displayed a pattern similar to that of LV dimensions, whereas anti-inflammatory (IL-10), anti-apoptotic (Bcl-2), and anti-fibrotic (Smad1/5, BMP-2) indices showed a pattern similar to that of LV performance among the four groups (all p < 0.05). Angiogenesis biomarkers at protein (CXCR4, SDF-1α, VEGF), cellular (CD31 +, CXCR4 +, SDF-1α +), and immunohistochemical (small vessels) levels, and cardiac stem cell markers (C-kit +, Sca-1 +) in infarct myocardium were highest in group 4, lowest in group 1, and significantly higher in group 3 than in group 2 (all p < 0.005).ConclusionPRF-embedded ADMSC is superior to direct ADMSC implantation in preserving LV function and attenuating LV remodeling. |
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Keywords: | Acute myocardial infarction Platelet-rich fibrin scaffold Adipose-derived mesenchymal stem cell Angiogenesis Left ventricular remodeling |
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