Therapeutic effects of a mesenchymal stem cell-based insulin-like growth factor-1/enhanced green fluorescent protein dual gene sorting system in a myocardial infarction rat model

摘要

The present study was conducted in order to improve gene expression efficiency of insulin-like growth factor-1 (IGF-1)-transfected mesenchymal stem cells (MSCs) using a non-viral carrier and a simplified method of dual gene selection. The therapeutic efficacy of this MSC-based IGF-1/enhanced green fluorescent protein (EGFP) dual gene sorting system was evaluated in a rat myocardial infarction (MI) model. IGF-1 and EGFP genes were expressed in MSCs in vitro. The purity of dual gene-expressing MSCs was 95.1% by fluorescence-activated cell sorting. Transfected MSCs injected into rats were identified based on green fluorescence, with an increased signal intensity observed in rats injected with sorted cells, compared with unsorted cells. IGF-1 expression levels were additionally increased in the sorted group, and decreases in infarct size, fibrotic area and fraction of apoptotic cells were observed. These results demonstrated that IGF-1 overexpression protects against fibrosis and apoptosis in the myocardium and reduces infarct size following MI. Additionally, the present vector sorting system may potentially be applied to other types of stem cell-based gene therapy.