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HSV-1 amplicon viral vector-mediated gene transfer to human bone marrow-derived mesenchymal stem cells

Cancer Gene Therapy volume 15, pages 553–562 (2008)Cite this article

Abstract

Human bone marrow-derived mesenchymal stem cells (BM-hMSCs) are nonhematopoietic stem cells that have the potential to differentiate into adipocytes, osteocytes and chondrocytes. Because of its propensity to migrate to the sites of injury and the ability to expand them rapidly, BM-hMSCs have been exploited as potential gene transfer vehicles to deliver therapeutic genes. Herein, we evaluated the feasibility of employing herpes simplex virus type I (HSV-1) amplicon viral vector as a gene delivery vector to BM-hMSCs. High transduction efficiencies were consistently observed in different isolates of BM-hMSCs following infection with HSV-1 amplicon viral vectors. Furthermore, we demonstrated that transduction with HSV-1 amplicon viral vector did not alter the intrinsic properties of the BM-hMSCs. The morphology and cellular proliferation of the transduced BM-hMSCs were not altered. Chromosomal stability, as confirmed by karyotyping and soft agar colony assays, of the transduced BM-hMSCs was not affected. Similarly, transduction with HSV-1 amplicon viral vectors has no effect on the pluripotent differentiation potential and the tumor tropism of BM-hMSCs. Taken together, these results demonstrated that BM-hMSCs could be transduced efficiently by HSV-1 amplicon viral vector in an ‘inert’ manner and thus enable strategies to express potential therapeutic genes in BM-hMSCs.

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Acknowledgements

We thank Dr Y Saeki (Ohio State University Medical Center, Columbus) for providing the pHGCX HSV-1 amplicon vector and the fHSVΔpac270+; Dr G Wang for assistance in intracranial tumor implantation and Mr KC Sia for assistance in packaging of the HSV-1 amplicon viral vectors.

This research is supported by grants from the SingHealth Foundation and National Medical Research Council, Singapore. IAW Ho is supported by the Singapore Millennium Foundation.

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Authors and Affiliations

  1. Division of Cellular and Molecular Research, Laboratory of Cancer Gene Therapy, National Cancer Centre, Singapore, Singapore

    I A W Ho, L Miao, K M Hui & P Y P Lam

  2. Division of BioEngineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, Singapore

    K Y W Chan & P Cheang

  3. Research and Development Unit, National Heart Centre, Singapore, Singapore

    W S N Shim

  4. Department of Orthopedic, Singapore General Hospital, Singapore, Singapore

    C M Guo

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  1. I A W Ho
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Correspondence to P Y P Lam.

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Ho, I., Chan, K., Miao, L. et al. HSV-1 amplicon viral vector-mediated gene transfer to human bone marrow-derived mesenchymal stem cells. Cancer Gene Ther 15, 553–562 (2008). https://doi.org/10.1038/cgt.2008.27

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