Faezeh Vakhshiteh1, Soheila Rahmani2, Seyed Nasser Ostad3, Zahra Madjd4, Rassoul Dinarvand5, Fatemeh Atyabi6. 1. Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. 2. Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran. 3. Department of Toxicology & Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. 4. Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. 5. Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. 6. Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: atyabifa@tums.ac.ir.
Abstract
AIMS: Exosomes hold great promise as bio-inspired delivery vehicles. Mesenchymal stem cells (MSCs) are recognized for their potential to yield huge quantities of exosomes. We aimed to investigate the potential use of modified exosomes derived from genetically modified dental pulp MSCs (DPSCs) as a carrier to deliver tumor suppressor miR-34a to repress proliferation of breast carcinoma cells. MATERIALS AND METHODS: miR-34a-overexpressing DPSCs were prepared using XMIRXpress-34a lentivectors. The anticancer effects of the miR-34a-loaded exosomes were evaluated on breast carcinoma cells through apoptosis, migration, and invasion assays. Given the structural similarity between exosomes and liposomes, we compared the exosome-mediated miRNA delivery efficiency with that of liposomes. KEY FINDINGS: Our data demonstrated that genetically modified DPSCs were capable of secretion of exosomes enriched with therapeutic miRNAs and presented the feasibility of application of exosome-based vehicle for gene delivery. SIGNIFICANCE: We showed the potential of MSC-derived exosomes as a tool for delivery of miRNAs in vitro. Nevertheless, optimizing gene-loading approaches is required before exosomes can be intended as a miRNA carrier for therapeutic applications.
AIMS: Exosomes hold great promise as bio-inspired delivery vehicles. Mesenchymal stem cells (MSCs) are recognized for their potential to yield huge quantities of exosomes. We aimed to investigate the potential use of modified exosomes derived from genetically modified dental pulp MSCs (DPSCs) as a carrier to deliver tumor suppressor miR-34a to repress proliferation of breast carcinoma cells. MATERIALS AND METHODS:miR-34a-overexpressing DPSCs were prepared using XMIRXpress-34a lentivectors. The anticancer effects of the miR-34a-loaded exosomes were evaluated on breast carcinoma cells through apoptosis, migration, and invasion assays. Given the structural similarity between exosomes and liposomes, we compared the exosome-mediated miRNA delivery efficiency with that of liposomes. KEY FINDINGS: Our data demonstrated that genetically modified DPSCs were capable of secretion of exosomes enriched with therapeutic miRNAs and presented the feasibility of application of exosome-based vehicle for gene delivery. SIGNIFICANCE: We showed the potential of MSC-derived exosomes as a tool for delivery of miRNAs in vitro. Nevertheless, optimizing gene-loading approaches is required before exosomes can be intended as a miRNA carrier for therapeutic applications.
Authors: Andrew E Massey; Shabnam Malik; Mohammad Sikander; Kyle A Doxtater; Manish K Tripathi; Sheema Khan; Murali M Yallapu; Meena Jaggi; Subhash C Chauhan; Bilal B Hafeez Journal: Int J Mol Sci Date: 2021-05-17 Impact factor: 5.923