Interleukin 10-Secreting MSCs via TALEN-Mediated Gene Editing Attenuates Left Ventricular Remodeling after Myocardial Infarction

Cell Physiol Biochem. 2019;52(4):728-741. doi: 10.33594/000000051.

Abstract

Background/aims: Stem cells or progenitor cells have been demonstrated as a novel alternative for cell therapy; however, their sustained efficacy is still debated. This study aimed to evaluate whether interleukin 10 (IL-10) gene-edited amniotic mesenchymal stem cells (AMM/I) contribute to left ventricular (LV) function and remodeling after acute myocardial infarction (AMI).

Methods: The IL-10 gene was integrated into the genomic locus of AMM via transcription activator-like effector nucleases (TALEN) and AMM/I were intramyocardially transplanted into AMI mice models. Cardiac function, quantitative polymerase chain reaction, histology, capillary density, and apoptosis assays were performed.

Results: AMM/I transplantation significantly suppressed infiltrated CD68 positive or F4/80 positive inflammatory cells and reduced the expression of pro-inflammatory factors in the infarcted myocardium. In addition, significantly improved LV function and reduced infarct size was noted in mice model with AMM/I transplantation than in those given AMM. Moreover, AMM/I highly inhibited cell apoptosis and increased capillary density in the infarcted myocardium.

Conclusion: Our study demonstrated that AMM/I recruitment played favorable roles in the early restoration of LV function and remodeling by suppressing inflammation and enhancing cardiac protection and capillary density.

Keywords: Acute myocardial infarction; Amniotic mesenchymal stem cells; Anti-inflammation; Cardiac remodeling; Genome editing.

MeSH terms

  • Amnion / cytology
  • Animals
  • Cluster Analysis
  • Disease Models, Animal
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / metabolism
  • Gene Editing*
  • Humans
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Nude
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Infarction / therapy*
  • Myocardium / metabolism
  • Myocardium / pathology
  • Transcription Activator-Like Effector Nucleases / genetics
  • Transcriptome
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Ventricular Remodeling*

Substances

  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • Fibroblast Growth Factor 2
  • Interleukin-10
  • Transcription Activator-Like Effector Nucleases