Immunomodulatory Effects Of Cisplatin On hMSC in vitro

Introduction:

The use of cytostatic drugs like Cisplatin is a common therapeutic strategy for head and neck carcinoma. The tumor microenvironment, including human mesenchymal stem cells (hMSC), is crucial for carcinogenesis. Besides its cytotoxicity, Cisplatin in subtoxic concentrations shows immunomodulatory effects. The objective of this study was to investigate the immunomodulatory impact of Cisplatin on hMSC regarding the expression of cytokines and growth factors in vitro.

Methods:

hMSCs of bone marrow tissue were used. Cells were incubated with Cisplatin in subtoxic concentrations for 24 hours and further cultivated for 72 hours. Cells in the control group were cultivated without Cisplatin. After the cultivation, PGE2, TGF-ß, IL-6 und Ido, which are known to be important factors for the immunomodulation, were quantified by ELISA. To avoid toxic effects of Cisplatin on hMSC, cell proliferation was measured by FACS and scratch-assays.

Results:

A significant increase of PGE2, TGF-ß, IL-6 und Ido could be shown after incubation with low-dosed Cisplatin compared to the control group. Toxic effects of Cisplatin to hMSC could neither be shown regarding proliferation, migration nor viabililty.

Conclusion:

Cisplatin leads even in non-cytotoxic concentration to an increased secretion of immunomodulatory cytokines in hMSC. In future studies the immunomodulatory effects of Cisplatin, especially in co-culture with lymphocytes as effectorcells of the cytokines will be analysed to evaluate new strategies for cancer treatment.

Publication History

Publication Date:
23 April 2019 (online)