TY - JOUR
T1 - Potent bystander effect and tumor tropism in suicide gene therapy using stem cells from human exfoliated deciduous teeth
AU - Horikawa, Makoto
AU - Koizumi, Shinichiro
AU - Oishi, Tomoya
AU - Yamamoto, Taisuke
AU - Ikeno, Masashi
AU - Ito, Masahiko
AU - Yamasaki, Tomohiro
AU - Amano, Shinji
AU - Sameshima, Tetsuro
AU - Mitani, Yasuyuki
AU - Otani, Yoshihiro
AU - Yan, Yuanqing
AU - Suzuki, Tetsuro
AU - Namba, Hiroki
AU - Kurozumi, Kazuhiko
N1 - Funding Information:
This work was supported by Hamamatsu University School of Medicine (HUSM) Grant-in-Aid. This study was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Numbers JP20K09325 (KK), JP19K09523 (TS).
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2022
Y1 - 2022
N2 - Herpes simplex virus thymidine kinase (HSVTK)/ganciclovir (GCV) suicide gene therapy has a long history of treating malignant gliomas. Recently, stem cells from human exfoliated deciduous teeth (SHED), which are collected from deciduous teeth and have excellent harvestability, ethical aspects, and self-renewal, have been attracting attention mainly in the field of gene therapy. In the present study, we assessed SHED as a novel cellular vehicle for suicide gene therapy in malignant gliomas, as we have previously demonstrated with various cell types. SHED was transduced with the HSVTK gene (SHEDTK). In vitro experiments showed a significant bystander effect between SHEDTK and glioma cell lines in coculture. Furthermore, apoptotic changes caused by caspase 3/7 activation were simultaneously observed in SHEDTK and glioma cells. Mice implanted with a mixture of U87 and SHEDTK and treated with intraperitoneal GCV survived for longer than 100 days. Additionally, tumors in treatment model mice were significantly reduced in size during the treatment period. SHEDTK implanted at the contralateral hemisphere migrated toward the tumor crossing the corpus callosum. These results suggested that SHEDTK-based suicide gene therapy has potent tumor tropism and a bystander-killing effect, potentially offering a new promising therapeutic modality for malignant gliomas.
AB - Herpes simplex virus thymidine kinase (HSVTK)/ganciclovir (GCV) suicide gene therapy has a long history of treating malignant gliomas. Recently, stem cells from human exfoliated deciduous teeth (SHED), which are collected from deciduous teeth and have excellent harvestability, ethical aspects, and self-renewal, have been attracting attention mainly in the field of gene therapy. In the present study, we assessed SHED as a novel cellular vehicle for suicide gene therapy in malignant gliomas, as we have previously demonstrated with various cell types. SHED was transduced with the HSVTK gene (SHEDTK). In vitro experiments showed a significant bystander effect between SHEDTK and glioma cell lines in coculture. Furthermore, apoptotic changes caused by caspase 3/7 activation were simultaneously observed in SHEDTK and glioma cells. Mice implanted with a mixture of U87 and SHEDTK and treated with intraperitoneal GCV survived for longer than 100 days. Additionally, tumors in treatment model mice were significantly reduced in size during the treatment period. SHEDTK implanted at the contralateral hemisphere migrated toward the tumor crossing the corpus callosum. These results suggested that SHEDTK-based suicide gene therapy has potent tumor tropism and a bystander-killing effect, potentially offering a new promising therapeutic modality for malignant gliomas.
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U2 - 10.1038/s41417-022-00527-5
DO - 10.1038/s41417-022-00527-5
M3 - Article
C2 - 36076062
AN - SCOPUS:85137567000
SN - 0929-1903
JO - Cancer Gene Therapy
JF - Cancer Gene Therapy
ER -
