Adipose-derived mesenchymal stem cells embedded in platelet-rich fibrin scaffolds promote angiogenesis, preserve heart function, and reduce left ventricular remodeling in rat acute myocardial infarction

Am J Transl Res. 2015 May 15;7(5):781-803. eCollection 2015.

Abstract

Objective: This study tested the hypothesis that autologous adipose-derived mesenchymal stem cells (ADMSCs) embedded in platelet-rich fibrin (PRF) can significant promote myocardial regeneration and repair after acute myocardial infarction (AMI).

Summary background: With avoiding the needle-related complications, PRF-embedded autologous ADMSCs graft provides a new effective stem cell-based therapeutic strategy for myocardial repair.

Methods: Adult male Sprague-Dawley rats were equally divided (n = 8 per group) into group 1 (sham-operated), group 2 (AMI by ligating left coronary artery), group 3 (AMI+ PRF), and group 4 (AMI+PRF-embedded autologous ADMSCs). RPF with or without ADMSCs was patched on infarct area 1h after AMI induction. All animals were sacrificed on day 42 after echocardiography.

Results: Left ventricular (LV) dimension and infarct/fibrotic areas were lowest in group 1, highest in group 2, in group 3 higher than in group 4, whereas LV performance and wall thickness exhibited a reversed pattern in all groups (all p < 0.001). Protein expressions of inflammatory (MMP-9, IL-1β), oxidative, apoptotic (Bax, cleaved PARP), fibrotic (Smad 3, TFG-β), hypertrophic (β-MHC), and heart failure (BNP) biomarkers displayed an identical pattern in infarct/fibrotic areas, whereas the protein expressions of anti-inflammatory (IL-10), anti-apoptotic (Bcl-2), anti-fibrotic (Smad1/5, BMP-2) biomarkers and α-MHC showed an opposite pattern (all p < 0.01). Angiogenic activities (c-Kit+, Sca-1+, CD31+, SDF-1α+, CXCR4+ cells; protein expressions of SDF-1α, CXCR4, VEGF) were highest in group 4 and lowest in group 1 (all p < 0.001).

Conclusion: ADMSCs embedded in PRF offered significant benefit in preserving LV function and limiting LV remodeling after AMI.

Keywords: Acute myocardial infarction; engineered tissue; mesenchymal stem cells; platelet-rich fibrin.