Mesenchymal stem cells used as carrier cells of oncolytic adenovirus results in enhanced oncolytic virotherapy

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dc.contributor.authorMahasa, Khaphetsi Josephen_ZA
dc.contributor.authorDe Pillis, Lisetteen_ZA
dc.contributor.authorOuifki, Rachiden_ZA
dc.contributor.authorEladdadi, Aminaen_ZA
dc.contributor.authorMaini, Philipen_ZA
dc.contributor.authorYoon, A-Rumen_ZA
dc.contributor.authorYun, Chae-Oken_ZA
dc.date.accessioned2020-04-16T08:17:07Z
dc.date.available2020-04-16T08:17:07Z
dc.date.issued2020-01-16
dc.descriptionCITATION: Mahasa, K. J. et al. 2020. Mesenchymal stem cells used as carrier cells of oncolytic adenovirus results in enhanced oncolytic virotherapy. Nature Scientific Reports, 10:425, doi:10.1038/s41598-019-57240-x.
dc.descriptionThe original publication is available at https://www.nature.com
dc.description.abstractMesenchymal stem cells (MSCs) loaded with oncolytic viruses are presently being investigated as a new modality of advanced/metastatic tumors treatment and enhancement of virotherapy. MSCs can, however, either promote or suppress tumor growth. To address the critical question of how MSCs loaded with oncolytic viruses affect virotherapy outcomes and tumor growth patterns in a tumor microenvironment, we developed and analyzed an integrated mathematical-experimental model. We used the model to describe both the growth dynamics in our experiments of firefly luciferase-expressing Hep3B tumor xenografts and the effects of the immune response during the MSCs-based virotherapy. We further employed it to explore the conceptual clinical feasibility, particularly, in evaluating the relative significance of potential immune promotive/suppressive mechanisms induced by MSCs loaded with oncolytic viruses. We were able to delineate conditions which may significantly contribute to the success or failure of MSC-based virotherapy as well as generate new hypotheses. In fact, one of the most impactful outcomes shown by this investigation, not inferred from the experiments alone, was the initially counter-intuitive fact that using tumor-promoting MSCs as carriers is not only helpful but necessary in achieving tumor control. Considering the fact that it is still currently a controversial debate whether MSCs exert a pro- or anti-tumor action, mathematical models such as this one help to quantitatively predict the consequences of using MSCs for delivering virotherapeutic agents in vivo. Taken together, our results show that MSC-mediated systemic delivery of oncolytic viruses is a promising strategy for achieving synergistic anti-tumor efficacy with improved safety profiles.en_ZA
dc.description.sponsorshipNational Research Foundation of Korea
dc.description.sponsorshipKorea Drug Development Fund
dc.description.sponsorshipDST/NRF SARChI Chair in Mathematical Models and Methods in Biosciences and Bioengineering at the University of Pretoria
dc.description.urihttps://www.nature.com/articles/s41598-019-57240-x#citeas
dc.description.versionPublisher's version
dc.format.extent13 pages
dc.identifier.citationMahasa, K. J. et al. 2020. Mesenchymal stem cells used as carrier cells of oncolytic adenovirus results in enhanced oncolytic virotherapy. Nature Scientific Reports, 10:425, doi:10.1038/s41598-019-57240-x.
dc.identifier.issn2045-2322 (online)
dc.identifier.otherdoi:10.1038/s41598-019-57240-x
dc.identifier.urihttp://hdl.handle.net/10019.1/107700
dc.language.isoen_ZAen_ZA
dc.publisherSpringer Nature
dc.rights.holderAuthors retain copyright
dc.subjectMesenchymal stem cells-based virotherapyen_ZA
dc.subjectAdenovirusen_ZA
dc.subjectDNA virusesen_ZA
dc.subjectOncogenic viruses -- Mathematical modelsen_ZA
dc.subjectTumors -- Treatmenten_ZA
dc.titleMesenchymal stem cells used as carrier cells of oncolytic adenovirus results in enhanced oncolytic virotherapyen_ZA
dc.typeArticleen_ZA
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