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Efficacy of IFN-γ-Primed Umbilical Cord-Derived Mesenchymal Stem Cells on Temporomandibular Joint Osteoarthritis

  • Original Article
  • Published:
Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease affecting the cartilage and subchondral bone, leading to temporomandibular joint pain and dysfunction. The complex nature of TMJOA warrants effective alternative treatments, and mesenchymal stem cells (MSCs) have shown promise in regenerative therapies. The aim of this study is twofold: firstly, to ascertain the optimal interferon-gamma (IFN-γ)-primed MSC cell line for TMJOA treatment, and secondly, to comprehensively evaluate the therapeutic efficacy of IFN-γ-primed mesenchymal stem cells derived from the human umbilical cord matrix in a rat model of TMJOA.

Methods:

We analyzed changes in the expression of several key genes associated with OA protection in MSC-secreted compounds. Following this, we performed co-culture experiments using a transwell system to predict gene expression changes in primed MSCs in the TMJOA environment. Subsequently, we investigated the efficacy of the selected IFN-γ-primed human umbilical cord matrix-derived MSCs (hUCM-MSCs) for TMJOA treatment in a rat model.

Results:

IFN-γ-primed MSCs exhibited enhanced expression of IDO, TSG-6, and FGF-2. Moreover, co-culturing with rat OA chondrocytes induced a decrease in pro-inflammatory and extracellular matrix degradation factors. In the rat TMJOA model, IFN-γ-primed MSCs with elevated IDO1, TSG-6, and FGF2 expression exhibited robust anti-inflammatory and therapeutic capacities, promoting the improvement of the inflammatory environment and cartilage regeneration.

Conclusion:

These findings underscore the importance of prioritizing the mitigation of the inflammatory milieu in TMJOA treatment and highlight IFN-γ-primed MSCs secreting these three factors as a promising, comprehensive therapeutic strategy.

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Data availability statements

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

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Acknowledgements

This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: H21C0168).

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Authors and Affiliations

  1. Biomedical Engineering Research Center, Asan Medical Center, Asan Institute for Life Sciences, Seoul, Korea

    Hyunjeong Kim & Bu-Kyu Lee

  2. Asan Medical Center, AMIST, College of Medicine, University of Ulsan, Seoul, Korea

    Yerin Kim, So-Yeon Yun & Bu-Kyu Lee

  3. Department of Oral and Maxillofacial Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

    Bu-Kyu Lee

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Contributions

HK was responsible for drafting the manuscript, analyzing and interpreting the data, as well as conducting and designing this study. YK and SYY contributed to the execution of the study. BKL is the corresponding author, responsible for the conception and critical revision of the article.

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Correspondence to Bu-Kyu Lee.

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The authors have no financial conflicts of interest.

Ethical statement

This work was approved by the Public Institutional Bioethics Committee designated by the MOHW (IRB no. 2020-1825-011). All animal experiments were performed in accordance with relevant guidelines and regulations of the Institutional Animal Care and Use Committee of Asan Medical Center (authorization no. 2021-12-208), which is accredited for laboratory animal care by the Ministry of Food and Drug Safety of South Korea.

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Kim, H., Kim, Y., Yun, SY. et al. Efficacy of IFN-γ-Primed Umbilical Cord-Derived Mesenchymal Stem Cells on Temporomandibular Joint Osteoarthritis. Tissue Eng Regen Med 21, 473–486 (2024). https://doi.org/10.1007/s13770-023-00620-2

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