Reovirus safety study for proliferation and differentiation of human adipose-derived mesenchymal stem cells

Park, Jeong‐Soo; Kim, Manbok

doi:10.1007/s12275-017-6542-0

Cited by 8 publications

(5 citation statements)

References 18 publications

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“…The results showed that AD-MSCs lost their differentiation potential, followed by the loosing of a typical fibroblast-like spindle shape, leading to elevated morphological abnormality, as shown in the different conditions such as changing condition media, when infected with reovirus, while the surface markers did not change significantly. The previous report by Park and Kim 21 showed that MSCs retained their differentiation potency to adipogenic and osteogenic lineages after infection with reovirus. Other studies showed that cytomegalovirus and human immunodeficiency virus infection affected MSCs differentiation potential into osteocyte and adipocyte and also may cause changes in the surface markers of MSCs.…”

Section: Discussionmentioning

confidence: 89%

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

Banijamali

Soleimanjahi

Soudi

et al. 2021

J of Cellular Biochemistry

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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-β1) 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-β 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.

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Section: Discussionmentioning

confidence: 89%

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

Banijamali

Soleimanjahi

Soudi

et al. 2021

J of Cellular Biochemistry

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“…The mechanism for why reovirus can infect some cancers and not others remains undefined and we speculated that an investigation into the similarities between stem cells and cancer cells provides a new avenue of investigation into what regulates this phenomenon. Although sensitivity of adult stem cells to reovirus has been investigated previously, particularly as groups are interested in using mesenchymal stem cells as carrier cells to deliver virus [ 75 , 76 ], no studies have investigated the sensitivity of pluripotent stem cells to reovirus. The first objective of this work was therefore to investigate both murine and human stem cell responses to reoviral infection.…”

Section: Resultsmentioning

confidence: 99%

“…Reovirus is capable of infecting and lysing cancer cells and cancer stem cells, and, as shown here, healthy ESCs. Intriguingly, adult (mesenchymal and hematopoietic) stem cells appear to be refractory to infection [ 76 , 86 ]. In light of the recent view that pluripotency induction shares similar pathways with carcinogenesis, it is possible to suggest that the same subset of genes that are activated in some cancers may also be up-regulated in pluripotent cells, thereby rendering them permissive to infection.…”

Section: Discussionmentioning

confidence: 99%

Modulation of Reoviral Cytolysis (II): Cellular Stemness

Bourhill

Rohani

Kumar

et al. 2023

Viruses

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Oncolytic viruses (OVs) are an emerging cancer therapeutic that are intended to act by selectively targeting and lysing cancerous cells and by stimulating anti-tumour immune responses, while leaving normal cells mainly unaffected. Reovirus is a well-studied OV that is undergoing advanced clinical trials and has received FDA approval in selected circumstances. However, the mechanisms governing reoviral selectivity are not well characterised despite many years of effort, including those in our accompanying paper where we characterize pathways that do not consistently modulate reoviral cytolysis. We have earlier shown that reovirus is capable of infecting and lysing both certain types of cancer cells and also cancer stem cells, and here we demonstrate its ability to also infect and kill healthy pluripotent stem cells (PSCs). This led us to hypothesize that pathways responsible for stemness may constitute a novel route for the modulation of reoviral tropism. We find that reovirus is capable of killing both murine and human embryonic and induced pluripotent stem cells. Differentiation of PSCs alters the cells’ reoviral-permissive state to a resistant one. In a breast cancer cell line that was resistant to reoviral oncolysis, induction of pluripotency programming rendered the cells permissive to cytolysis. Bioinformatic analysis indicates that expression of the Yamanaka pluripotency factors may be associated with regulating reoviral selectivity. Mechanistic insights from these studies will be useful for the advancement of reoviral oncolytic therapy.

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“…Park and Kim investigated reoviral replication in mesenchymal stem cell populations and found that these cells were still capable of proliferation and differentiation following reoviral infection. They concluded that mesenchymal stem cell populations would be a potential carrier for reovirus to enhance systemic infections [ 51 ].…”

Section: Deliverymentioning

confidence: 99%

Going (Reo)Viral: Factors Promoting Successful Reoviral Oncolytic Infection

Bourhill

Mori

Rancourt

et al. 2018

Viruses

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Oncolytic viruses show intriguing potential as cancer therapeutic agents. These viruses are capable of selectively targeting and killing cancerous cells while leaving healthy cells largely unaffected. The use of oncolytic viruses for cancer treatments in selected circumstances has recently been approved by the Food and Drug Administration (FDA) of the US and work is progressing on engineering viral vectors for enhanced selectivity, efficacy and safety. However, a better fundamental understanding of tumour and viral biology is essential for the continued advancement of the oncolytic field. This knowledge will not only help to engineer more potent and effective viruses but may also contribute to the identification of biomarkers that can determine which patients will benefit most from this treatment. A mechanistic understanding of the overlapping activity of viral and standard chemotherapeutics will enable the development of better combinational approaches to improve patient outcomes. In this review, we will examine each of the factors that contribute to productive viral infections in cancerous cells versus healthy cells. Special attention will be paid to reovirus as it is a well-studied virus and the only wild-type virus to have received orphan drug designation by the FDA. Although considerable insight into reoviral biology exists, there remain numerous deficiencies in our understanding of the factors regulating its successful oncolytic infection. Here we will discuss what is known to regulate infection as well as speculate about potential new mechanisms that may enhance successful replication. A joint appreciation of both tumour and viral biology will drive innovation for the next generation of reoviral mediated oncolytic therapy.

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Reovirus safety study for proliferation and differentiation of human adipose-derived mesenchymal stem cells

Cited by 8 publications

References 18 publications

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

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

Modulation of Reoviral Cytolysis (II): Cellular Stemness

Going (Reo)Viral: Factors Promoting Successful Reoviral Oncolytic Infection

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