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Paracrine Factors Released from Tonsil-Derived Mesenchymal Stem Cells Inhibit Proliferation of Hematological Cancer Cells Under Hyperthermia in Co-culture Model

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Abstract

Mesenchymal stem cells (MSCs) are promising biological therapeutic candidates in cancer treatment. As a source of MSCs, palatine tonsil tissue is one of the secondary lymphoid organs that form an essential part of the immune system, and the relation between the secondary lymphoid organs and cancer progression leads us to investigate the effect of tonsil-derived MSCs (T-MSC) on cancer treatment. We aimed to determine the anti-tumoral effects of T-MSCs cultured at the febrile temperature (40 °C) on hematological cancer cell lines. The co-culture of cancer cells with T-MSCs was carried out under fever and normal culture conditions, and then the cell viability was determined by cell counting. In addition, apoptosis rate and cell cycle arrest were determined by flow cytometry. We confirmed the apoptotic effect of T-MSC co-culture at the transcriptional level by using real-time polymerase chain reaction (RT-PCR). We found that co-culture of cancer cells with T-MSCs significantly decreased the viable cell number under the febrile and normal culture conditions. Besides, the T-MSC co-culture induced apoptosis on K562 and MOLT-4 cells and induced the cell cycle arrest at the G2/M phase on MOLT-4 cells. The apoptotic effect of T-MSC co-culture under febrile stimulation was confirmed at the transcriptional level. Our study has highlighted the anti-tumoral effect of the cellular interaction between the T-MSCs and human hematological cancer cells during in vitro co-culture under hyperthermia.

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Acknowledgements

We thank Assoc. Dr. Fatih Kocabaş, Yeditepe University Department of Genetics and Bioengineering faculty member for generously providing hematological cancer cell lines. In addition, we thank Dr. Gökhan Akgül and Assoc. Dr. Gültekin Ozan Küçük for assisting in the supply of tonsil tissue.

Funding

This work was funded by Ondokuz Mayıs University, Scientific Research Project Office, Turkey.

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  1. Stem Cell Research & Application Center, Ondokuz Mayıs University, Kurupelit Campus, 55139, Atakum, Samsun, Turkey

    Melek Yuce & Esra Albayrak

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MY: conceptualization, investigation, methodology, data curation, validation, funding acquisition, project administration, resources, writing and original draft preparation; EA: conceptualization, investigation, methodology, data curation, validation and original draft preparation. All authors read and approved the final manuscript.

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Correspondence to Melek Yuce.

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Ethics Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Clinic Research Ethics Committee of the Ondokuz Mayıs University of A (No. 2021/347).

Informed Consent Statement

To isolate human tonsil-derived mesenchymal stem cells, the tonsil tissues were obtained from the donors who have undergone tonsillectomy with donor’s consent and approval of OMU clinic research ethics committee (Decision number: 2021/347).

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The authors declare no competing interests.

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Yuce, M., Albayrak, E. Paracrine Factors Released from Tonsil-Derived Mesenchymal Stem Cells Inhibit Proliferation of Hematological Cancer Cells Under Hyperthermia in Co-culture Model. Appl Biochem Biotechnol (2023). https://doi.org/10.1007/s12010-023-04757-7

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