DNA-binding Cell-penetrating Peptide-based TRAIL Over-expression in Adipose Tissue-derived Mesenchymal Stem Cells Inhibits Glioma U251MG Growth

Abstract

Background/aim: Genetic manipulation of stem cells using non-viral vectors is still limited due to low transfection efficiency. We investigated whether the DNA-binding cell-permeation peptides (CPP) can enhance the transfection efficiency of non-viral vectors in adipose tissue-derived mesenchymal stem cells (ASCs) and whether ASCs over-expressing TRAIL through CPP can inhibit the growth of glioma U251MG cells in vitro and in vivo.

Materials and methods: ASCs were genetically engineered to over-express TRAIL by using CPP, pCMV3-TRAIL and lipid-based transfection reagents (X-tremeGENE).

Results: The transfection efficiency of ASCs increased by approximately 7% using CPP; 53.9% of ASCs were transfected and TRAIL expression in ASCs increased by approximately 3 times compared to X-tremeGENE alone. ASCs over-expressing TRAIL using CPP inhibited growth of glioma U251MG cells both in vitro and in the U251MG xenograft model.

Conclusion: CPP can be used as an enhancer for genetically manipulating ASCs and tumor treatment.

Keywords: Adipose tissue-derived mesenchymal stem cells; cell permeation peptide; genetic engineering; glioma; tumor necrosis factor-related apoptosis-inducing ligand.