Tissue Eng Regen Med.  2024 Apr;21(3):473-486. 10.1007/s13770-023-00620-2.

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

Affiliations
  • 1Biomedical Engineering Research Center, Asan Medical Center, Asan Institute for Life Sciences, Seoul, Korea
  • 2Asan Medical Center, AMIST, College of Medicine, University of Ulsan, Seoul, Korea
  • 3Department of Oral and Maxillofacial Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

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.

Keyword

Temporomandibular joint osteoarthritis; Human umbilical cord matrix-derived MSC; IFN-γ-primed MSCs; Anti-inflammatory; Therapeutic potential
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