Mesenchymal stem cell origin contributes to the antitumor effect of oncolytic virus carriers

Oncolytic virotherapy shows promise as a cancer treatment approach; however, its systemic application is hindered by antibody neutralization. This issue can be overcome by using mesenchymal stem cells (MSCs) as carrier cells for oncolytic viruses (OVs). However, it remains elusive whether MSC source influences the antitumor effect. Here, we demonstrate that their source affects the migration ability and oncolytic activity of OV-loaded MSCs. Among human MSCs derived from different tissues, bone marrow-derived MSCs (BMMSCs) showed a high migration ability toward cancer cells in two- and three-dimensional MSC-cancer cell co-culture models. Comprehensive gene expression and Gene Ontology-based functional analyses suggested that genes involved in cell migration and cytokine response influence the cancer-specific tropism of BMMSCs. Furthermore, MSC origin affected the susceptibility to OVs, including cytotoxicity resistance and OV release from MSCs. MSC-mediated OV delivery significantly increased the viral spread and antitumor activity compared with delivery by OVs alone, and OV-loaded BMMSCs demonstrated the most potent antitumor effect among OV-loaded MSCs. Our results offer promising insights into cancer gene therapy with carrier cells and can help with the selection of an appropriate MSC source for MSC-based OV therapy.