Mesenchymal stem cells support delivery and boost the efficacy of oncolytic reoviruses in TC-1 tumor cells.

Cancer has remained a major health problem around the world. Mesenchymal stem cells (MSCs)-based therapy exhibits a therapeutic effect via different mechanisms. By using MSCs as carrier cells, the major problem of clearance of oncolytic viruses is resolved by neutralizing antibodies before they react with cancer cells. The aim of this study was to characterize the effect of infected MSCs by reovirus type-3 Dearing (T3D) for in vitro cancer therapy. Adipose-derived MSCs (AD-MSCs) were infected with reovirus T3D and its biological properties were evaluated. Then, the effects of reovirus-infected AD-MSCs on cytokine profile, nitric oxide (NO) production, and apoptosis induction in TC-1 cells were assessed. Our results indicated that the differentiation potential of AD-MSCs was affected by reovirus. However, phenotypes were not affected after infection. Then, the effects of reovirus-infected AD-MSCs in TC-1 cells showed an increased amount of tumor necrosis factor-alpha (TNF-α) and NO production and a decreased amount of transforming growth factor-beta 1 (TGF-ß1) and interleukin-10 (IL-10). Moreover, apoptosis significantly increased via coculturing of TC-1 cells with infected AD-MSCs, compared with control, and both internal and external apoptosis pathways are activated in experimental groups. In conclusion, the data showed that with increasing TNF-α and NO production and reducing IL-10 and TGF-ß production, AD-MSCs can enhance the oncolytic effect of reovirus in cancer cells. Furthermore, the results suggested that AD-MSCs can be used as effective carrier cells candidate for reovirus T3D to maximize their anticancer cell activity.