Abstract
Purpose: Reovirus type 3 Dearing (ReoT3D), a wild type oncolytic virus (OV) from the Reoviridae family, kills KRAS mutant cancer cells. However, the use of OVs has faced with some limitations such as immune responses, and delivery of OVs to the tumor sites in systemic therapy. To solve this, and also to increase the anti-cancer effects of these OVs, mesenchymal stem cells (MSCs) might be used as an effective vehicle for OVs delivery. In this study, we examined the anti-cancer effects of human adipose derived-MSCs (AD-MSCs) as a vehicle of ReoT3D against human glioblastoma cells. Methods: Here, AD-MSCs were characterized and toxicity of ReoT3D on them was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Then, capability of AD-MSCs for virus production was assessed by real-time polymerase chain reaction (PCR), and different in vitro anti-cancer experiments were applied for our anti-cancer purposes.Results: Our results from toxicity assay revealed that the isolated and provoked AD-MSCs were resistant to nontoxic concentration multiplicity of infection (MOI) >1 pfu/cells of ReoT3D. In addition, the results indicated that AD-MSCs were susceptible for virus life cycle complementation and were capable for production of virus progenies. Furthermore, our results showed that AD-MSCs had oncolysis effects and increased the anti-cancer effects of ReoT3D. Conclusion: AD-MSCs as a susceptible host for oncolytic reovirus could increase the anti-cancer activity of this OV against glioblastoma multiforme (GBM) cell line.
Highlights
Glioblastoma multiforme (GBM) is one of the most common and devastating cancers of brain and central nervous system (CNS).[1,2,3] Surgery, radiotherapy and chemotherapy are conventional approaches used for treatment of GMB
Materials and Methods Cell culture The human glioblastoma U251 cell line and murine L929 cell line were cultured in high glucose Dulbecco’s modified Eagle medium (DMEM) (Sigma, USA) that supplemented with 10% of fetal bovine serum (FBS) (Gibco, USA), 1X of Non-Essential Amino Acids solution (NEAA) (Sigma, USA) and glutamine (Glu) (Sigma, USA) and 1% penicillin and streptomycin (Sigma, USA)
AD-mesenchymal stem cells (MSCs) cells proved by flow cytometry, Alizarin-red, and Oil red staining according to previous studies.[29,30]
Summary
Glioblastoma multiforme (GBM) is one of the most common and devastating cancers of brain and central nervous system (CNS).[1,2,3] Surgery, radiotherapy and chemotherapy (such as temozolomide) are conventional approaches used for treatment of GMB. Statistics showed that the patients suffering from GMB only have 15 months median survival rate and GMB has still been considered as incurable disease.[4,5] finding of effective approaches for precise treatment of the disease is an urgent need. Oncolytic viruses (OVs) due to having selectively targeting and replication in canner cells have been introduced as a new effective anti-cancer agent.[6] Recently, the clinical therapeutic usage of OVs against cancer cells has gained a great attention.[7] OVs may be natured or engineered with tropism for cancer cells that selectively replicate, which kill cells and spread in the tumor environment.[6,8]
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