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

doi:10.1631/jzus.B2300928

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

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Research Article | Updated：2025-08-25

Mitochondria derived from human embryonic stem cell-derived mesenchymal stem cells alleviate the inflammatory response in human gingival fibroblasts
Mitochondria derived from human embryonic stem cell-derived mesenchymal stem cells alleviate the inflammatory response in human gingival fibroblasts
人胚胎干细胞衍生间充质干细胞来源的线粒体减轻人牙龈成纤维细胞的炎症反应
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) Vol. 26, Issue 8, Pages: 778-788(2025)
Affiliations：

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
Funds：
DOI：10.1631/jzus.B2300928
CLC：
CSTR：
Received：21 December 2023，

Revised：16 July 2024，

Published Online：08 August 2025，

Published：25 August 2025
Accepted：

高碧聪,沈晨露,吕柯佳等.人胚胎干细胞衍生间充质干细胞来源的线粒体减轻人牙龈成纤维细胞的炎症反应[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(08):778-788.

Bicong GAO, Chenlu SHEN, Kejia LV, et al. Mitochondria derived from human embryonic stem cell-derived mesenchymal stem cells alleviate the inflammatory response in human gingival fibroblasts[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(8): 778-788.
高碧聪,沈晨露,吕柯佳等.人胚胎干细胞衍生间充质干细胞来源的线粒体减轻人牙龈成纤维细胞的炎症反应[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(08):778-788. DOI： 10.1631/jzus.B2300928.

Bicong GAO, Chenlu SHEN, Kejia LV, et al. Mitochondria derived from human embryonic stem cell-derived mesenchymal stem cells alleviate the inflammatory response in human gingival fibroblasts[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(8): 778-788. DOI： 10.1631/jzus.B2300928.

摘要

牙周炎是一种由细菌和过度宿主免疫反应引起的常见口腔疾病。干细胞疗法是一种治疗牙周炎的策略，但其相关机制较为复杂。本研究旨在探索人胚胎干细胞衍生间充质干细胞（hESC-MSCs）来源的线粒体治疗牙周炎的潜力。本研究发现牙周炎患者的牙龈组织线粒体结构异常，并通过5 μg/mL脂多糖（LPS）刺激人牙龈成纤维细胞（HGFs）24小时以构建细胞损伤模型。与对照组相比，在使用hESC-MSCs或从hESC-MSCs提取的线粒体进行处理后，HGFs的炎症基因表达减少，三磷酸腺苷（ATP）水平升高，活性氧物种（ROS）生成减少，以及线粒体功能增强。经流式细胞术测定，分离线粒体的平均转移效率为8.93%。此外，对LPS诱导的牙周炎小鼠进行局部线粒体注射治疗后，牙龈组织中炎症基因表达减少，但线粒体的数量和长宽比均有所增加。本研究结果表明，hESC-MSCs来源的线粒体可减轻炎症反应，并改善HGFs的线粒体功能，提示线粒体在hESC-MSCs和HGFs间的转移是干细胞治疗作用的潜在机制。

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.

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references

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Division of Medical Genetics and Genomics, The Children’s Hospital, Zhejiang University School of Medicine /National Clinical Research Center for Child Health

Institute of Genetics and Department of Human Genetics, Zhejiang University School of Medicine

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