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Updated: Aug 8, 2025

A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells
Published on: May 6, 2018
Oncolytic Effect of a Recombinant Vesicular Stomatitis Virus Encoding a Tumor-suppressor MicroRNA in an Osteosarcoma
Tomohiko Sakuda1, Tadahiko Kubo2, Muhammad Phetrus Johan3
1Department of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan; saakuuda@yahoo.co.jp.
Background/Aim:
Attempts have been made to enhance treatment with vesicular stomatitis virus (VSV) for osteosarcoma. We have previously shown that VSV incorporated with miRNA143 enhanced the antitumor effect at some doses; however, the range of the doses was narrow. This has not been evaluated in vivo, and the synergistic effect of this antitumor effect in animals is unknown. The purpose of the study was to evaluate the oncolytic effect of VSV-miRNA on osteosarcoma cells in vivo.
Materials And Methods:
A novel oncolytic VSV was developed by incorporating the tumor-suppressor microRNA143 (rVSV-miR143). In order to compare the antitumor effects of administration methods (intravenous and intratumoral administration) of rVSV-miR143 with those of VSV, a comparative analysis of primary tumor volume, metastatic lesions and survival rate was performed in mouse models of osteosarcoma.
Results:
Following intratumoral injection, rVSV-miR143 showed a significant reduction in primary tumor volume, but no significant difference was observed in metastatic lesions and survival rate compared to VSV. Following intravenous injection, rVSV-miR143 revealed no significant difference in primary tumor volume, metastatic lesion and survival rate compared to VSV.
Conclusion:
VSV incorporating tumor-suppressor miRNA143 demonstrated a slightly synergistic antitumor effect on osteosarcoma in vivo.
Insights
Vesicular stomatitis virus (VSV) engineered with microRNA143 showed a modest synergistic antitumor effect against osteosarcoma in vivo. Intratumoral delivery significantly reduced primary tumor volume, but did not impact metastasis or survival rates.
Area of Science:
- Oncolytic virotherapy
- Gene therapy
- Cancer research
Background:
- Vesicular stomatitis virus (VSV) has been explored for osteosarcoma treatment.
- Previous studies indicated VSV with microRNA143 (VSV-miRNA143) enhanced antitumor effects in vitro, but within a narrow dose range.
- The in vivo efficacy and synergistic effects of VSV-miRNA143 in osteosarcoma models remained unevaluated.
Purpose of the Study:
- To evaluate the in vivo oncolytic effect of VSV-miRNA143 on osteosarcoma.
- To compare the antitumor efficacy of different administration routes (intravenous vs. intratumoral) of VSV-miRNA143 against standard VSV.
Main Methods:
- A recombinant VSV incorporating tumor-suppressor microRNA143 (rVSV-miR143) was developed.
- Comparative analysis of primary tumor volume, metastatic lesions, and survival rates in osteosarcoma mouse models.
- Evaluation of both intratumoral and intravenous administration of rVSV-miR143.
Main Results:
- Intratumoral administration of rVSV-miR143 led to a significant reduction in primary tumor volume compared to VSV.
- No significant differences in metastatic lesions or survival rates were observed between rVSV-miR143 and VSV following intratumoral injection.
- Intravenous administration of rVSV-miR143 showed no significant difference in primary tumor volume, metastatic lesions, or survival rates compared to VSV.
Conclusions:
- VSV incorporating tumor-suppressor microRNA143 exhibits a mild synergistic antitumor effect in vivo.
- Intratumoral delivery of rVSV-miR143 shows potential for primary tumor volume reduction in osteosarcoma.
- Further optimization is needed to enhance the impact on metastasis and survival rates.
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