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Updated: Feb 14, 2026

Plaquing of Herpes Simplex Viruses
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Plaquing of Herpes Simplex Viruses

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Regulation of proliferation and functioning of transplanted cells by using herpes simplex virus thymidine kinase gene

Mari Tsujimura1, Kosuke Kusamori1, Chihiro Oda2

  • 1Department of Biopharmaceutics, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan; Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|February 20, 2018
PubMed

Insights

This study demonstrates that the herpes simplex virus thymidine kinase (HSVtk) suicide gene combined with ganciclovir (GCV) effectively controls transplanted insulin-secreting cells. This approach improves safety and therapeutic potential for cell-based therapies.

Area of Science:

  • Biomedical Engineering
  • Cell Therapy
  • Gene Therapy

Background:

  • Cell transplantation offers therapeutic potential but faces challenges with uncontrolled cell proliferation and function.
  • Regulating transplanted cell behavior is crucial for preventing adverse effects and enhancing therapeutic outcomes.

Purpose of the Study:

  • To investigate the use of the herpes simplex virus thymidine kinase (HSVtk) suicide gene and ganciclovir (GCV) to control insulin-secreting cells post-transplantation.
  • To assess the safety and efficacy of this gene-drug system in a mouse model of diabetes.

Main Methods:

  • Transfected mouse pancreatic beta cell line MIN6 cells with the HSVtk gene to create MIN6/HSVtk cells.
  • Evaluated GCV's effect on MIN6/HSVtk cell proliferation in vitro.
  • Transplanted MIN6 or MIN6/HSVtk cells into streptozotocin-induced diabetic mice and administered GCV.

Main Results:

  • GCV suppressed MIN6/HSVtk cell proliferation in a dose-dependent manner, with 0.25 μg/mL GCV maintaining cell numbers for 16 days.
  • Mice receiving MIN6 cells showed hypoglycemia, regardless of GCV.
  • Mice receiving MIN6/HSVtk cells and daily GCV (50 mg/kg) maintained normal blood glucose levels (around 150 mg/dL).

Conclusions:

  • The HSVtk/GCV system effectively controls the proliferation and function of transplanted insulin-secreting cells.
  • This method significantly enhances the safety and therapeutic utility of cell-based therapies for diabetes.
  • Gene-directed suicide systems offer a promising strategy for managing transplanted cell behavior.
Keywords:
Cell regulationCell-based therapyGanciclovirHerpes simplex virus thymidine kinaseSuicide gene

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