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.
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
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
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.