Suicide Gene Therapy Mediated with Exosomes Produced by Mesenchymal Stem/Stromal Cells Stably Transduced with HSV Thymidine Kinase.
Andrea PastorakovaJana JakubechovaUrsula AltanerovaČestmír AltanerPublished in: Cancers (2020)
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.
Keyphrases
- mesenchymal stem cells
- umbilical cord
- stem cells
- bone marrow
- cell therapy
- copy number
- herpes simplex virus
- cell death
- genome wide
- endothelial cells
- genome wide identification
- single cell
- cell cycle arrest
- gene expression
- cancer therapy
- pluripotent stem cells
- oxidative stress
- drug induced
- transcription factor
- high glucose
- climate change
- cell proliferation
- endoplasmic reticulum stress