Mitochondria derived from human embryonic stem cell-derived mesenchymal stem cells alleviate the inflammatory response in human gingival fibroblasts.

Bicong GAO; Chenlu SHEN; Kejia LV; Xuehui LI; Yongting ZHANG; Fan SHI; Hongyan DIAO; Hua YAO

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Mitochondria derived from human embryonic stem cell-derived mesenchymal stem cells alleviate the inflammatory response in human gingival fibroblasts.

Author: Bicong GAO ¹ ; Chenlu SHEN ¹ ; Kejia LV ¹ ; Xuehui LI ² ; Yongting ZHANG ² ; Fan SHI ² ; Hongyan DIAO ³ ; Hua YAO ⁴
Author Information

1. Department of Stomatology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
2. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
3. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China. yaohua@zju.edu.cn, diaohy@zju.edu.cn.
4. Department of Stomatology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China. yaohua@zju.edu.cn.
Publication Type:Journal Article
Keywords: Human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs); Inflammatory response; Mitochondrial dysfunction; Mitochondrial transfer; Periodontal disease
MeSH: Humans; Gingiva/cytology*; Fibroblasts/metabolism*; Mitochondria/physiology*; Mesenchymal Stem Cells/cytology*; Animals; Periodontitis/therapy*; Mice; Reactive Oxygen Species/metabolism*; Inflammation; Lipopolysaccharides; Human Embryonic Stem Cells/cytology*; Cells, Cultured; Adenosine Triphosphate/metabolism*; Male
From: Journal of Zhejiang University. Science. B 2025;26(8):778-788
CountryChina
Language:English
Abstract: Periodontitis is a common oral disease caused by bacteria coupled with an excessive host immune response. Stem cell therapy can be a promising treatment strategy for periodontitis, but the relevant mechanism is complicated. This study aimed to explore the therapeutic potential of mitochondria from human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs) for the treatment of periodontitis. The gingival tissues of periodontitis patients are characterized by abnormal mitochondrial structure. Human gingival fibroblasts (HGFs) were exposed to 5 μg/mL lipopolysaccharide (LPS) for 24 h to establish a cell injury model. When treated with hESC-MSCs or mitochondria derived from hESC-MSCs, HGFs showed reduced expression of inflammatory genes, increased adenosine triphosphate (ATP) level, decreased reactive oxygen species (ROS) production, and enhanced mitochondrial function compared to the control. The average efficiency of isolated mitochondrial transfer by hESC-MSCs was determined to be 8.93%. Besides, a therapy of local mitochondrial injection in mice with LPS-induced periodontitis showed a reduction in inflammatory gene expression, as well as an increase in both the mitochondrial number and the aspect ratio in gingival tissues. In conclusion, our results indicate that mitochondria derived from hESC-MSCs can reduce the inflammatory response and improve mitochondrial function in HGFs, suggesting that the transfer of mitochondria between hESC-MSCs and HGFs serves as a potential mechanism underlying the therapeutic effect of stem cells.