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

Int J Cardiol. 2014 May 15;173(3):410-23. doi: 10.1016/j.ijcard.2014.03.015. Epub 2014 Mar 14.

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.

Keywords: Acute myocardial infarction; Adipose-derived mesenchymal stem cell; Angiogenesis; Left ventricular remodeling; Platelet-rich fibrin scaffold.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / transplantation*
  • Animals
  • Blood Platelets*
  • Fibrin / administration & dosage*
  • Male
  • Mesenchymal Stem Cell Transplantation / methods*
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / therapy*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Scaffolds*
  • Treatment Outcome

Substances

  • Fibrin