Direct implantation versus platelet-rich fibrin-embedded adipose-derived mesenchymal stem cells in treating rat acute myocardial infarction

作者:Sun, Cheuk Kwan; Zhen, Yen Yi; Leu, Steve; Tsai, Tzu Hsien; Chang, Li Teh; Sheu, Jiunn Jye; Chen, Yung Lung; Chua, Sarah; Chai, Han Tan; Lu, Hung I; Chang, Hsueh Wen; Lee, Fan Yen; Yip, Hon Kan*
来源:International Journal of Cardiology, 2014, 173(3): 410-423.
DOI:10.1016/j.ijcard.2014.03.015

摘要

Background: This 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. Methods: Twenty-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. Results: LV 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-1 beta, MMP-9), apoptosis (mitochondrial Bax, cleaved PARP), fibrosis (Smad3, TGF-beta), and pressure-overload biomarkers (BNP, MHC-beta) 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-1 alpha, VEGF), cellular (CD31 , CXCR4 , SDF-1 alpha ), 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). Conclusion: PRF-embedded ADMSC is superior to direct ADMSC implantation in preserving LV function and attenuating LV remodeling.