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Updated: Jun 7, 2025

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Mesenchymal stem cell origin contributes to the antitumor effect of oncolytic virus carriers

Makoto Sukegawa1,2,3, Yoshitaka Miyagawa1, Seiji Kuroda1

  • 1Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.

Molecular Therapy. Oncology
|November 18, 2024
PubMed

Insights

Mesenchymal stem cells (MSCs) can deliver oncolytic viruses (OVs) for cancer therapy. Bone marrow-derived MSCs (BMMSCs) show superior migration and antitumor effects when loaded with OVs, enhancing cancer gene therapy.

Area of Science:

  • Oncology
  • Stem Cell Biology
  • Gene Therapy

Background:

  • Oncolytic virotherapy (OV) offers a promising cancer treatment strategy.
  • Systemic OV delivery is limited by antibody neutralization.
  • Mesenchymal stem cells (MSCs) are explored as carriers to overcome OV delivery challenges.

Purpose of the Study:

  • To investigate if the source of mesenchymal stem cells (MSCs) impacts their efficacy as carriers for oncolytic viruses (OVs).
  • To evaluate the migration ability and antitumor activity of OV-loaded MSCs from different human tissue sources.

Main Methods:

  • Co-culture models (2D and 3D) were used to assess MSC migration towards cancer cells.
  • Gene expression and Gene Ontology analyses were performed to understand MSC tropism.
  • Cytotoxicity, OV release, and antitumor effects of OV-loaded MSCs were evaluated.

Main Results:

  • Bone marrow-derived MSCs (BMMSCs) exhibited enhanced migration to cancer cells compared to MSCs from other tissues.
  • MSC origin influenced OV susceptibility, including resistance to cytotoxicity and OV release.
  • OV-loaded BMMSCs demonstrated the most potent antitumor activity, significantly improving viral spread and efficacy.

Conclusions:

  • The source of MSCs significantly affects their function as OV carriers.
  • BMMSCs are a superior choice for developing effective MSC-based OV cancer therapies.
  • These findings provide crucial insights for optimizing cancer gene therapy strategies using carrier cells.
Keywords:
MT: Regular IssueOV-loaded MSCscancer spheroidsmesenchymal stem cellsoncolytic herpes simplex virusthree-dimensional culture

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