Image-guided stem cells with functionalized self-assembling peptide nanofibers for treatment of acute myocardial infarction in a mouse model

Am J Transl Res. 2017 Aug 15;9(8):3723-3731. eCollection 2017.

Abstract

Aim: To investigate the survival of bone marrow mesenchymal stem cells (BMSCs) and the therapeutic effect for acute myocardial infarction (AMI) after co-transplantation with the functionalized self-assembling peptide nanofiber RAD/PRG or RAD/KLT.

Methods: AMI of balb/c mice was induced. Mice were randomly divided into four groups, and received treatment of phosphate buffered saline (PBS) (Group A), GFP/Fluc-BMSCs (Group B), GFP/Fluc-BMSCs + RAD/PRG (Group C), and GFP/Fluc-BMSCs + RAD/KLT (Group D), respectively. Bioluminescence imaging (BLI) was performed on day 1 (d-1), d-4, d-7, d-10, and d-13 after transplantation. Magnetic resonance imaging (MRI) was performed at baseline (d-4 before transplantation) and d-29 after treatment. Mice were euthanized on d-29 following treatment. Paraffin sections were obtained from the top, mid and bottom part of the infarcted region along the long-axis of the heart. Hematoxylin and eosin (HE) staining and immunohistochemical staining were performed. The infarct ratio micro-vascular density (MVD) was quantified.

Results: There was a significant higher of BLI signal intensity of BMSCs in Group C than that in Group B (d-4, 9713±320 vs. 8164±378, P=0.0008; d-7, 6489±241 vs. 5417±361, P=0.0026; d-10, 3768±255 vs. 0, P < 0.0001). The left ventricular ejection fraction (LVEF) via MRI examination was significantly improved in both Group C and Group D. Infarct ratio and MVD were significantly improved in both Group C and Group D.

Conclusion: Our data highlights BMSCs combining functionalized self-assembling peptide nanofibers RAD/PRG or RAD/KLT as promising therapy for AMI.

Keywords: Stem cell therapy; acute myocardial infarction; functionalized self-assembling peptide nanofibers; molecular imaging.