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北京大学学报（医学版） ›› 2026, Vol. 58 ›› Issue (2): 285-289. doi: 10.19723/j.issn.1671-167X.2026.02.010

• 工作综述 • 上一篇    下一篇

干细胞功能调控在颅颌面组织再生修复中的研究进展

张晗*, 杨馥嘉*, 杨瑞莉*()   

  1. 北京大学口腔医学院·口腔医院正畸科, 国家口腔医学中心, 国家口腔疾病临床医学研究中心, 口腔生物材料和数字诊疗装备国家工程研究中心, 口腔数字医学北京市重点实验室, 北京 100081
  • 收稿日期:2025-09-09 出版日期:2026-04-18 发布日期:2026-03-12
  • 通讯作者: 杨瑞莉
  • 作者简介:

    * These authors contributed equally to this work

  • 基金资助:
    国家重点研发计划(2022YFA1105800); 国家自然科学基金(U2330102); 北京市自然科学基金(7232219)

Progress in regulating stem cell functions for repair and regeneration of craniomaxillofacial tissues

Han ZHANG, Fujia YANG, Ruili YANG*()   

  1. Department of Orthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digi-tal Medical Devices & Beijing Key Laboratory of Digital Stomatology, Beijing 100181, China
  • Received:2025-09-09 Online:2026-04-18 Published:2026-03-12
  • Contact: Ruili YANG
  • Supported by:
    the National Key Research and Development Program of China(2022YFA1105800); the National Natural Science Foundation of China(U2330102); the Beijing Natural Science Foundation(7232219)

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摘要：

颅颌面组织再生修复是口腔与再生医学领域的关键挑战。间充质基质/干细胞(mesenchymal stromal/stem cells, MSCs)作为核心效应细胞, 其功能受代谢、表观遗传与免疫网络的多维精密调控。本文系统综述了MSCs在颅颌面组织再生中的功能调控机制, 重点探讨了力学刺激、代谢重编程、H2S气体信号以及表观遗传修饰对MSCs干性维持、定向分化及免疫调节功能的影响。同时, 阐述了MSCs通过外泌体等载体与免疫细胞相互作用, 共同调控骨稳态与再生进程的双向机制。文末展望了基于MSCs及其工程化外泌体的靶向治疗策略所面临的挑战与临床转化前景, 旨在为颅颌面缺损的再生修复提供新的见解。

关键词: 间充质干细胞, 再生, 组织工程, 颅骨, 面骨

Abstract:

Craniofacial tissue regeneration remains a pivotal challenge in oral and regenerative medicine. Mesenchymal stem/stromal cells (MSCs) are central effector cells in this process, and their functions are regulated by a sophisticated, multidimensional network. This article provides a comprehensive overview of the regulatory mechanisms governing MSCs in craniofacial regeneration. We highlight the interactive roles of metabolism, epigenetics, and immunity in precisely controlling MSC stemness, lineage-specific differentiation, and immunomodulatory capabilities. Key regulatory dimensions are explored in detail. Metabolic reprogramming, such as serine one-carbon metabolism and mitochondrial dynamics under hyperosmotic stress, couples energy production with epigenetic modifications to dictate MSC fate. The gasotransmitter hydrogen sulfide (H2S) exerts tissue-specific effects, modulating immunoregulation via the Fas/FasL axis in gingival MSCs and promoting odontogenic differentiation in dental pulp stem cells (DPSCs) via the transient receptor potential action channel subfamily vanilloid member 1 (TRPV1)/β-catenin pathway. Epigenetic mechanisms, including DNA demethylation by ten-eleven translocation (TET) enzymes and chromatin remodeling by special AT-rich sequence-binding protein 2 (SATB2), finely tune MSC homeostasis and differentiation potential. Crucially, MSCs do not function in isolation. Their bidirectional crosstalk with immune cells, mediated by exosomes and soluble factors, is essential for bone homeostasis. Mechanical overloading can trigger MSCs to promote T helper 17 (Th17) cell polarization via metabolic reprogramming, exacerbating bone destruction. Conversely, H2S-modified exosomes from M2 macrophages can enhance MSC osteogenesis, demonstrating a synergistic metabolic-immune axis for bone regeneration. Exosomes themselves serve as versatile therapeutic carriers, capable of delivering miRNAs (e.g., miR-125a/b) or functional mitochondrial DNA to modulate immunity or repair cellular metabolism. The clinical translation of MSCs holds great promise for treating conditions like periodontitis and temporomandibular joint disorders. Advances in engineered exosomes and biomaterial carriers (e.g., hydrogels) offer strategies for targeted delivery and enhanced efficacy. Future research must focus on developing tissue-specific delivery systems, refining exosome engineering for precise cargo loading, and leveraging multi-omics technologies to decipher the complex stem cell niche. This progression from empi-rical application to rationally designed, precision therapies will be critical for addressing clinical challenges in craniofacial reconstruction.

Key words: Mesenchymal stem cells, Regeneration, Tissue engineering, Skull, Facial bones

中图分类号: 

  • R782

图1

干细胞功能调控示意图 MCP1, monocyte chemoattractant protein-1; MSCs, mesenchymal stromal/stem cells; PHGDH, phosphoglycerate dehydrogenase; SAM, S-adenosyl-methionine; TET, ten-eleven translocation; SATB2, special AT-rich sequence-binding protein 2."

1
Zhang H , Liu D , Wu T , et al. Exploring mesenchymal stem cell niches for regeneration[J]. Sci Bull, 2025, 70 (9): 1389- 1393.

doi: 10.1016/j.scib.2025.03.011
2
Xin T , Zhang T , Li Q , et al. A novel mutation of MSX1 in oligo-dontia inhibits odontogenesis of dental pulp stem cells via the ERK pathway[J]. Stem Cell Res Ther, 2018, 9 (1): 221.

doi: 10.1186/s13287-018-0965-3
3
Huang HM , Han CS , Cui SJ , et al. Mechanical force-promoted osteoclastic differentiation via periodontal ligament stem cell exosomal protein ANXA3[J]. Stem Cell Reports, 2022, 17 (8): 1842- 1858.

doi: 10.1016/j.stemcr.2022.06.006
4
Yang R , Yu T , Liu D , et al. Hydrogen sulfide promotes immunomodulation of gingiva-derived mesenchymal stem cells via the Fas/FasL coupling pathway[J]. Stem Cell Res Ther, 2018, 9 (1): 62.

doi: 10.1186/s13287-018-0804-6
5
Yang RL , Huang HM , Han CS , et al. Serine metabolism controls dental pulp stem cell aging by regulating the DNA methylation of p16[J]. J Dent Res, 2021, 100 (1): 90- 97.

doi: 10.1177/0022034520958374
6
Wang YM , Lin S , Chen LJ , et al. Mitochondrial components transferred by MSC-derived exosomes promoted bone regeneration under high salt microenvironment via DRP1/Wnt signaling[J]. Nano Res, 2024, 17 (9): 8301- 8315.

doi: 10.1007/s12274-024-6758-3
7
Yang R , Liu Y , Yu T , et al. Hydrogen sulfide maintains dental pulp stem cell function via TRPV1-mediated calcium influx[J]. Cell Death Discov, 2018, 4, 69.

doi: 10.1038/s41420-018-0071-4
8
Yang R , Yu T , Kou X , et al. Tet1 and Tet2 maintain mesenchymal stem cell homeostasis via demethylation of the P2rX7 promoter[J]. Nat Commun, 2018, 9 (1): 2143.

doi: 10.1038/s41467-018-04464-6
9
Yu T , Liu D , Zhang T , et al. Inhibition of Tet1- and Tet2-mediated DNA demethylation promotes immunomodulation of periodontal ligament stem cells[J]. Cell Death Dis, 2019, 10 (10): 780.

doi: 10.1038/s41419-019-2025-z
10
Xin T , Li Q , Bai R , et al. A novel mutation of SATB2 inhibits odontogenesis of human dental pulp stem cells through Wnt/β-catenin signaling pathway[J]. Stem Cell Res Ther, 2021, 12 (1): 595.

doi: 10.1186/s13287-021-02660-8
11
Zhou Y , Li M , Lin S , et al. Mechanical sensing protein PIEZO1 controls osteoarthritis via glycolysis mediated mesenchymal stem cells-Th17 cells crosstalk[J]. Cell Death Dis, 2025, 16 (1): 231.

doi: 10.1038/s41419-025-07577-1
12
Zhou YK , Han CS , Zhu ZL , et al. M2 exosomes modified by hydrogen sulfide promoted bone regeneration by moesin mediated endocytosis[J]. Bioact Mater, 2023, 31, 192- 205.
13
Yang R , Huang H , Cui S , et al. IFN-γ promoted exosomes from mesenchymal stem cells to attenuate colitis via miR-125a and miR-125b[J]. Cell Death Dis, 2020, 11 (7): 603.

doi: 10.1038/s41419-020-02788-0
14
Cui SJ , Zhang T , Fu Y , et al. DPSCs attenuate experimental progressive TMJ arthritis by inhibiting the STAT1 pathway[J]. J Dent Res, 2020, 99 (4): 446- 455.

doi: 10.1177/0022034520901710
15
Wei FL , Zhai Y , Wang TF , et al. Stem cell-homing biomimetic hydrogel promotes the repair of osteoporotic bone defects through osteogenic and angiogenic coupling[J]. Sci Adv, 2024, 10 (44): eadq6700.

doi: 10.1126/sciadv.adq6700
16
Chen P , Zhou YK , Han CS , et al. Stem cells from human exfoliated deciduous teeth alleviate liver cirrhosis via inhibition of gasdermin D-executed hepatocyte pyroptosis[J]. Front Immunol, 2022, 13, 860225.

doi: 10.3389/fimmu.2022.860225
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ISSN 1671-167X
CN 11-4691/R
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