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Updated: Aug 25, 2025
Assessment of the Immunomodulatory Properties of Human Mesenchymal Stem Cells MSCs
Published on: December 24, 2015
Comparison of Different Clinical Chemotherapeutical Agents' Toxicity and Cell Response on Mesenchymal Stem Cells and
Flóra Vajda1,2, Áron Szepesi1,3, György Várady1
1Institute of Enzymology, Research Centre for Natural Sciences, 1117 Budapest, Hungary.
Abstract:
Mesenchymal stem cells (MSCs) or fibroblasts are one of the most abundant cell types in the tumor microenvironment (TME) exerting various anti- and pro-apoptotic effects during tumorigenesis, invasion, and drug treatment. Despite the recently discovered importance of MSCs in tumor progression and therapy, the response of these cells to chemotherapeutics compared to cancer cells is rarely investigated. A widely accepted view is that these naive MSCs have higher drug tolerance than cancer cells due to a significantly lower proliferation rate. Here, we examine the differences and similarities in the sensitivity of MSCs and cancer cells to nine diverse chemotherapy agents and show that, although MSCs have a slower cell cycle, these cells are still sensitive to various drugs. Surprisingly, MSCs showed similar sensitivity to a panel of compounds, however, suffered fewer DNA double-stranded breaks, did not enter into a senescent state, and was virtually incapable of apoptosis. Our results suggest that MSCs and cancer cells have different cell fates after drug treatment, and this could influence therapy outcome. These findings could help design drug combinations targeting both MSCs and cancer cells in the TME.
Insights
Mesenchymal stem cells (MSCs) are sensitive to chemotherapy, but unlike cancer cells, they resist apoptosis and senescence. This difference in cell fate impacts therapeutic outcomes in the tumor microenvironment.
Area of Science:
- Cancer Biology
- Cellular Therapeutics
- Tumor Microenvironment (TME)
Background:
- Mesenchymal stem cells (MSCs) and fibroblasts are key components of the tumor microenvironment (TME).
- MSCs influence tumor progression, invasion, and response to drug treatment through anti- and pro-apoptotic effects.
- The differential response of MSCs versus cancer cells to chemotherapy remains under-investigated.
Purpose of the Study:
- To compare the sensitivity of MSCs and cancer cells to nine different chemotherapy agents.
- To investigate the distinct cellular fates of MSCs and cancer cells following chemotherapy exposure.
Main Methods:
- Treatment of MSCs and cancer cells with nine diverse chemotherapy agents.
- Assessment of drug sensitivity, DNA double-strand breaks, senescence, and apoptosis.
- Comparative analysis of cellular responses between MSCs and cancer cells.
Main Results:
- MSCs exhibit sensitivity to various chemotherapy drugs, contrary to the assumption of high drug tolerance.
- Despite similar sensitivity to some compounds, MSCs experienced fewer DNA double-strand breaks.
- MSCs demonstrated resistance to senescence and apoptosis, unlike cancer cells, after drug treatment.
Conclusions:
- MSCs and cancer cells undergo divergent cell fates post-chemotherapy.
- These differential responses may significantly influence overall therapy outcomes.
- Findings support the development of combination therapies targeting both cancer cells and MSCs within the TME.
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