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Phenotypic and functional alterations of bone marrow MSCs exposed to multiple myeloma cells

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Abstract

Backgrounds

The direct and indirect interactions between multiple myeloma (MM) cells and bone marrow mesenchymal stromal cells (MSCs) play crucial roles in the formation of the bone marrow environment, disease progression, and drug resistance development. However, it remains unclear how MM cells and MSCs individually influence each other to induce these phenomena.

Objective

In this study, we focused on observing changes in MSCs induced by MM cells. Changes in MSCs due to exposure to MM cells were observed by assessing cell proliferation, apoptosis, cell cycle, and morphology. Furthermore, the unique abilities of MSCs were confirmed through differentiation potential and MSC marker expression, along with the demonstration of senescence. Gene profiling was performed to elucidate the mechanisms underlying these changes.

Results

Co-culturing MM cells with MSCs did not alter the morphology or proliferation of MSCs but increased apoptosis. As apoptosis increased, damaged deoxyribonucleic acid (DNA) was repaired, leading to the activation of the cell cycle with an increase in the S phase, resulting in no significant changes in cell proliferation and morphology. Osteogenesis and adipogenesis generally decreased by co-culturing with MM cells, and senescence increased. Significant differences were observed in the expression of MSC marker genes. Gene profiling revealed changes in gene expression following osteogenic differentiation.

Conclusion

Based on these results, MSCs exposed to MM cells exhibited an increase in the S phase of the cell cycle, leading to the recovery of cells undergoing apoptosis. Osteogenesis and adipogenesis decreased, whereas senescence increased, suggesting that these changes were attributed to the overall MSC characteristics and genetic mechanisms.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The author(s) wish(es) to acknowledge the financial support of the Catholic Medical Center Research Foundation made in the program year of 2015. Also, this work was supported by the National Research Foundation (NRF) grant (No. 2022R1F1A1075163) funded by the MSIT of Korea (2022M3A9B6018217); and the Technology Innovation Program (No.20012378) funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea).

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Author notes

  1. Hye Joung Kim and So Young Eom contributed equally to this work.

Authors and Affiliations

  1. Institute of Chemical Engineering Convergence System, Korea University, Seoul, 02841, Republic of Korea

    Hye Joung Kim

  2. School of Mechanical Engineering, Korea University, Seoul, 02841, Republic of Korea

    So Young Eom, Hyunsoo Kim, Jihee Won & Seok Chung

  3. Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 34943, Republic of Korea

    Saeyeon Hwang

  4. KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea

    Seok Chung

  5. Center for Brain Technology, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea

    Seok Chung

  6. Department of Hematology, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Incheon, Republic of Korea

    Seung-Ah Yahng

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Contributions

HJK and S-AY designed the research study. SYE and SH performed the experiments. SYE and SH and HK analyzed the experiment data. HJK and S-AY and SYE interpreted data and wrote manuscript. According to the experimental contribution, HJK stated as the first co-first author.

Corresponding author

Correspondence to Seung-Ah Yahng.

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Conflict of interest

Hye Joung Kim declares that she has no conflict of interest. So Young Eom declares that she has no conflict of interest. Saeyeon Hwang declares that he has no conflict of interest. Hyunsoo Kim declares that he has no conflict of interest. Seok Chung declares that he has no conflict of interest. Seung-Ah Yahng declares that she has no conflict of interest.

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Kim, H.J., Eom, S.Y., Hwang, S. et al. Phenotypic and functional alterations of bone marrow MSCs exposed to multiple myeloma cells. Mol. Cell. Toxicol. (2023). https://doi.org/10.1007/s13273-023-00415-5

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