Prodrug suicide gene therapy for cancer targeted intracellular by mesenchymal stem cell exosomes
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
30098225
DOI
10.1002/ijc.31792
Knihovny.cz E-zdroje
- Klíčová slova
- Gene directed enzyme prodrug therapy, MSC suicide gene exosomes, mesenchymal stem cells, suicide gene,
- MeSH
- antimetabolity antitumorózní metabolismus farmakologie MeSH
- cytosindeaminasa genetika metabolismus MeSH
- exozómy genetika metabolismus MeSH
- flucytosin metabolismus MeSH
- fluorouracil metabolismus farmakologie MeSH
- fungální proteiny genetika metabolismus MeSH
- genetická terapie metody MeSH
- kvasinky genetika metabolismus MeSH
- lidé MeSH
- mezenchymální kmenové buňky metabolismus MeSH
- nádorové buněčné linie MeSH
- nádory prsu genetika metabolismus patologie MeSH
- pentosyltransferasy genetika metabolismus MeSH
- prekurzory léčiv metabolismus MeSH
- proliferace buněk účinky léků genetika MeSH
- transgeny sebevražedné genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antimetabolity antitumorózní MeSH
- cytosindeaminasa MeSH
- flucytosin MeSH
- fluorouracil MeSH
- fungální proteiny MeSH
- pentosyltransferasy MeSH
- prekurzory léčiv MeSH
- uracil phosphoribosyltransferase MeSH Prohlížeč
The natural behavior of mesenchymal stem cells (MSCs) and their exosomes in targeting tumors is a promising approach for curative therapy. Human tumor tropic mesenchymal stem cells (MSCs) isolated from various tissues and MSCs engineered to express the yeast cytosine deaminase::uracil phosphoribosyl transferase suicide fusion gene (yCD::UPRT-MSCs) released exosomes in conditional medium (CM). Exosomes from all tissue specific yCD::UPRT-MSCs contained mRNA of the suicide gene in the exosome's cargo. When the CM was applied to tumor cells, the exosomes were internalized by recipient tumor cells and in the presence of the prodrug 5-fluorocytosine (5-FC) effectively triggered dose-dependent tumor cell death by endocytosed exosomes via an intracellular conversion of the prodrug 5-FC to 5-fluorouracil. Exosomes were found to be responsible for the tumor inhibitory activity. The presence of microRNAs in exosomes produced from naive MSCs and from suicide gene transduced MSCs did not differ significantly. MicroRNAs from yCD::UPRT-MSCs were not associated with therapeutic effect. MSC suicide gene exosomes represent a new class of tumor cell targeting drug acting intracellular with curative potential.
Cancer Research Institute Biomedical Center Slovak Academy of Sciences Bratislava Slovakia
Department of Biology Faculty of Medicine in Pilsen Charles University Prague Pilsen Czech Republic
St Elisabeth Cancer Institute Stem Cell Preparation Department Bratislava Slovakia
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