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

Research output: Contribution to journalJournal Article peer-review

52 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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