Suicide Gene Therapy Mediated with Exosomes Produced by Mesenchymal Stem/Stromal Cells Stably Transduced with HSV Thymidine Kinase
Open Access
- 27 April 2020
- Vol. 12 (5), 1096
- https://doi.org/10.3390/cancers12051096
Abstract
Mesenchymal stem/stromal cells (MSCs) prepared from various human tissues were stably transduced with the suicide gene herpes simplex virus thymidine kinase (HSVTK) by means of retrovirus infection. HSVTK-transduced MSCs express the suicide gene and in prodrug ganciclovir (GCV) presence induced cell death by intracellular conversion of GCV to GCV-triphosphate. The homogenous population of HSVTK-MSCs were found to release exosomes having mRNA of the suicide gene in their cargo. The exosomes were easily internalized by the tumor cells and the presence of ganciclovir caused their death in a dose-dependent manner. Efficient tumor cell killing of glioma cell lines and primary human glioblastoma cells mediated by HSVTK-MSC exosomes is reported. Exosomes produced by suicide gene transduced MSCs represent a new class of highly selective tumor cell targeted drug acting intracellular with curative potential.Keywords
This publication has 30 references indexed in Scilit:
- Characterization of Mesenchymal Stem Cells of “No-Options” Patients with Critical Limb Ischemia Treated by Autologous Bone Marrow Mononuclear CellsPLOS ONE, 2013
- Human adipose tissue‐derived mesenchymal stem cells expressing yeast cytosinedeaminase::uracil phosphoribosyltransferase inhibit intracerebral rat glioblastomaInternational Journal of Cancer, 2011
- HSV-tk expressing mesenchymal stem cells exert bystander effect on human glioblastoma cellsCancer Letters, 2010
- Adipose Tissue–derived Mesenchymal Stem Cells Expressing Prodrug-converting Enzyme Inhibit Human Prostate Tumor GrowthMolecular Therapy, 2010
- Remission of Invasive, Cancer Stem-Like Glioblastoma Xenografts Using Lentiviral Vector-Mediated Suicide Gene TherapyPLOS ONE, 2009
- Cytosine deaminase expressing human mesenchymal stem cells mediated tumour regression in melanoma bearing miceThe Journal of Gene Medicine, 2008
- Prodrug cancer gene therapyCancer Letters, 2008
- Bystander Killing of Malignant Glioma by Bone Marrow–derived Tumor-Infiltrating Progenitor Cells Expressing a Suicide GeneMolecular Therapy, 2007
- Adipose Tissue–Derived Human Mesenchymal Stem Cells Mediated Prodrug Cancer Gene TherapyCancer Research, 2007
- A Phase III Clinical Evaluation of Herpes Simplex Virus Type 1 Thymidine Kinase and Ganciclovir Gene Therapy as an Adjuvant to Surgical Resection and Radiation in Adults with Previously Untreated Glioblastoma MultiformeHuman Gene Therapy, 2000