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Extracellular vesicles derived from dental mesenchymal stem/stromal cells with gemcitabine as a cargo have an inhibitory effect on the growth of pancreatic carcinoma cell lines in vitro.

作者信息

Klimova Daniela, Jakubechova Jana, Altanerova Ursula, Nicodemou Andreas, Styk Jakub, Szemes Tomas, Repiska Vanda, Altaner Cestmir

机构信息

Institute of Medical Biology, Genetics and Clinical Genetics, Comenius University in Bratislava, Bratislava, Slovakia.

Department of Stem Cell Preparation, St. Elisabeth Cancer Institute, Bratislava, Slovakia; Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Bratislava, Slovakia.

出版信息

Mol Cell Probes. 2023 Feb;67:101894. doi: 10.1016/j.mcp.2023.101894. Epub 2023 Jan 25.


DOI:10.1016/j.mcp.2023.101894
PMID:36706931
Abstract

Extracellular vesicles (EVs) are nowadays a target of interest in cancer therapy as a successful drug delivering tool. Based on their many beneficial biocompatible properties are designed to transport nucleic acids, proteins, various nanomaterials or chemotherapeutics. Extracellular vesicles derived from mesenchymal stem/stromal cells (MSCs) possess their tumor-homing abilities. This inspired us to engineer the MSC's EVs to be packed with chemotherapeutic agents and deliver it as a Trojan horse directly into tumor cells. In our study, human dental pulp MSCs (DP-MSCs) were cultivated with gemcitabine (GCB), which led to its absorption by the cells and subsequent secretion of the drug out into conditioned media in EVs. Concentrated conditioned media containing small EVs (potentially exosomes) significantly inhibited the cell growth of pancreatic carcinoma cell lines in vitro. DP-MSCs were simultaneously engineered to express a suicide gene fused yeast cytosinedeaminase:uracilphosphoribosyltransferase (yCD::UPRT). The product of the suicide gene converts non-toxic prodrug 5-fluorocytosine (5-FC) to highly cytotoxic chemotherapeutic drug 5-fluorouracil (5-FU) in the recipient cancer cells. Conversion of 5-FC to 5-FU had an additional effect on cancer cell's growth inhibition. Our results showed a therapeutic potential for DP-MSC-EVs to be designed for successful delivering of chemotherapeutic drugs, together with prodrug suicide gene therapy system.

摘要

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引用本文的文献

[1]
Gemcitabine and Flurbiprofen Enhance Cytotoxic Effects on Cancer Cell Lines Mediated by Mesenchymal Stem Cells.

Int J Mol Sci. 2025-6-27

[2]
Tailored Extracellular Vesicles from Dental Stem Cells: Advances in Specific Modifications for Enhanced Therapeutic Applications.

Int J Nanomedicine. 2025-6-26

[3]
Isolation methods of exosomes derived from dental stem cells.

Int J Oral Sci. 2025-6-16

[4]
Glioblastoma progression is hindered by melatonin-primed mesenchymal stromal cells through dynamic intracellular and extracellular reorganizations.

Theranostics. 2025-2-10

[5]
Engineered mesenchymal stem/stromal cells against cancer.

Cell Death Dis. 2025-2-19

[6]
Natural and Bioengineered Extracellular Vesicles in Diagnosis, Monitoring and Treatment of Cancer.

ACS Nano. 2025-2-18

[7]
Exosomes as promising frontier approaches in future cancer therapy.

World J Gastrointest Oncol. 2025-1-15

[8]
The crosstalk between primary MSCs and cancer cells in 2D and 3D cultures: potential therapeutic strategies and impact on drug resistance.

Stem Cells Transl Med. 2024-12-16

[9]
Human bone marrow mesenchymal stem cell-derived exosomes loaded with gemcitabine inhibit pancreatic cancer cell proliferation by enhancing apoptosis.

World J Gastrointest Oncol. 2024-9-15

[10]
Exosomes: Emerging Insights into the Progression of Pancreatic Cancer.

Int J Biol Sci. 2024-8-1

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