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

  • 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*
  • *Corresponding author for this work
  • I-Shou University
  • Chang Gung Memorial Hospital
  • Center for Translational Research in Biomedical Sciences
  • Meiho University
  • Chang Gung University
  • National Sun Yat-sen University

Research output: Contribution to journalJournal Article peer-review

54 Scopus citations

Abstract

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-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). Conclusion PRF-embedded ADMSC is superior to direct ADMSC implantation in preserving LV function and attenuating LV remodeling.

Original languageEnglish
Pages (from-to)410-423
Number of pages14
JournalInternational Journal of Cardiology
Volume173
Issue number3
DOIs
StatePublished - 15 05 2014

Keywords

  • Acute myocardial infarction
  • Adipose-derived mesenchymal stem cell
  • Angiogenesis
  • Left ventricular remodeling
  • Platelet-rich fibrin scaffold

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