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Reovirus safety study for proliferation and differentiation of human adipose-derived mesenchymal stem cells
Jeong-Soo Park , Manbok Kim
J. Microbiol. 2017;55(1):75-79.   Published online December 30, 2016
DOI: https://doi.org/10.1007/s12275-017-6542-0
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  • 8 Crossref
AbstractAbstract
Naturally occurring reoviruses are live replication-proficient viruses specifically infecting human cancer cells while sparing the normal counterparts. Stem cells can be highly susceptible to viral infection due to their innate high proliferation potential and other active signaling pathways of cells that might be involved in viral tropism. In the previous study, we showed that reoviruses could adversely affect murine embryonic stem cells’ integrity in vitro and in vivo. Oncolytic viruses, delivered systemically face many hurdles that also impede their localization and infection of, metastatic tumors, due to a variety of immune and physical barriers. To overcome such hurdles to systemic delivery, several studies supported the idea that certain types of cells, including mesenchymal stem cells, might play a role as cell carriers for oncolytic viruses. Thus, it would be interesting to examine whether human adult stem cells such as human adipose-derived mesenchymal stem cells could be saved by the reoviral challenge. In this study, we report that biological activities such as proliferation and multipotency of human adipose-derived stem cells are not affected by wild-type reovirus challenge as evidenced by survival, osteogenic and adipogenic differentiation potential assays following treatment with reoviruses. Therefore, unlike murine embryonic stem cells, our study strongly suggests that human adipose-derived adult stem cells could be spared in vivo during wild-type reoviral anti-cancer therapeutics in a clinical setting. Furthermore, the results support the possible clinical use of human adipose-derived stem cells as an effective cell carrier of oncolytic reovirus to maximize their tumor tropism and anti-tumor activity.

Citations

Citations to this article as recorded by  
  • Modulation of Reoviral Cytolysis (II): Cellular Stemness
    Tarryn Bourhill, Leili Rohani, Mehul Kumar, Pinaki Bose, Derrick Rancourt, Randal N. Johnston
    Viruses.2023; 15(7): 1473.     CrossRef
  • Mesenchymal stem cell carriers enhance antitumor efficacy induced by oncolytic reovirus in acute myeloid leukemia
    Xianyao Wang, Yichen Yang, Nianxue Wang, Xijun Wu, Jianwei Xu, Yanhua Zhou, Xing Zhao, Zhixu He
    International Immunopharmacology.2021; 94: 107437.     CrossRef
  • Mesenchymal stem cells support delivery and boost the efficacy of oncolytic reoviruses in TC‐1 tumor cells
    Razieh S. Banijamali, Hoorieh Soleimanjahi, Sara Soudi, Hesam Karimi
    Journal of Cellular Biochemistry.2021; 122(10): 1360.     CrossRef
  • Mesenchymal stem cells as carriers for systemic delivery of oncolytic viruses
    Agata Hadryś, Aleksander Sochanik, Grant McFadden, Joanna Jazowiecka-Rakus
    European Journal of Pharmacology.2020; 874: 172991.     CrossRef
  • Recent advances in targeting cancer stem cells using oncolytic viruses
    You-Ni Zhang, Shi-Bing Wang, Shu-Shu Song, Pei-Yang Hu, Yu-Cheng Zhou, Yi-Ping Mou, Xiao-Zhou Mou
    Biotechnology Letters.2020; 42(6): 865.     CrossRef
  • The oncolytic efficacy and safety of avian reovirus and its dynamic distribution in infected mice
    Ruimin Cai, Guangyuan Meng, Yi Li, Wenyang Wang, Youxiang Diao, Shuping Zhao, Qiang Feng, Yi Tang
    Experimental Biology and Medicine.2019; 244(12): 983.     CrossRef
  • Going (Reo)Viral: Factors Promoting Successful Reoviral Oncolytic Infection
    Tarryn Bourhill, Yoshinori Mori, Derrick Rancourt, Maya Shmulevitz, Randal Johnston
    Viruses.2018; 10(8): 421.     CrossRef
  • Primary lymphocyte infection models for KSHV and its putative tumorigenesis mechanisms in B cell lymphomas
    Sangmin Kang, Jinjong Myoung
    Journal of Microbiology.2017; 55(5): 319.     CrossRef
Review
Reovirus and Tumor Oncolysis
Manbok Kim , Young-Hwa Chung , Randal N. Johnston
J. Microbiol. 2007;45(3):187-192.
DOI: https://doi.org/2544 [pii]
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AbstractAbstract
REOviruses (Respiratory Enteric Orphan viruses) are ubiquitous, non-enveloped viruses containing 10 segments of double-stranded RNA (dsRNA) as their genome. They are common isolates of the respiratory and gastrointestinal tract of humans but are not associated with severe disease and are therefore considered relatively benign. An intriguing characteristic of reovirus is its innate oncolytic potential, which is linked to the transformed state of the cell. When immortalized cells are transfected in vitro with activated oncogenes such as Ras, Sos, v-erbB, or c-myc, they became susceptible to reovirus infection and subsequent cellular lysis, indicating that oncogene signaling pathways are exploited by reovirus. This observation has led to the use of the virus in clinical trials as an anti-cancer agent against oncogenic tumors. In addition to the exploitation of oncogene signaling, reovirus may further utilize host immune responses to enhance its antitumor activity in vivo due to its innate interferon induction ability. Reovirus is, however, not entirely benign to immunocompromised animal models. Reovirus causes so-called “black feet syndrome” in immunodeficient mice and can also harm neonatal animals. Because cancer patients often undergo immunosuppression due to heavy chemo/radiation-treatments or advanced tumor progression, this pathogenic response may be a hurdle in virus-based anticancer therapies. However, a genetically attenuated reovirus variant derived from persistent reovirus infection of cells in vitro is able to exert potent anti-tumor activity with significantly reduced viral pathogenesis in immunocompromised animals. Importantly, in this instance the attenuated reovirus maintains its oncolytic potential while significantly reducing viral pathogenesis in vivo.

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