切换至 "中华医学电子期刊资源库"

中华口腔医学研究杂志(电子版) ›› 2026, Vol. 20 ›› Issue (05) : 383 -388. doi: 10.3877/cma.j.issn.119285-20260410-00037

专家笔谈

干细胞微球在牙髓再生领域的研究进展
王晓怡, 孙喆轶, 霍丽珺†()   
  1. 昆明医科大学附属口腔医院牙体牙髓病科,云南省口腔医学重点实验室,昆明 650106
  • 收稿日期:2026-04-10 出版日期:2026-10-01
  • 通信作者: 霍丽珺

Research progress on stem cell spheroids in the field of dental pulp regeneration

Xiaoyi Wang, Zheyi Sun, Lijun Huo†()   

  1. Department of Endodontics, Kunming Medical University Affiliated Stomatological Hospital, Yunnan Key Laboratory of Stomatology, Kunming 650106, China
  • Received:2026-04-10 Published:2026-10-01
  • Corresponding author: Lijun Huo
  • Supported by:
    Scientific Research Fund of Yunnan Provincial Department of Education(2023Y0664); Science and Technology Program of Yunnan Provincial Department of Science and Technology(202201AY070001-171); Scientific Research Project of Yunnan Provincial Clinical Medical Center(2024YNLCYXZX0307)
引用本文:

王晓怡, 孙喆轶, 霍丽珺. 干细胞微球在牙髓再生领域的研究进展[J/OL]. 中华口腔医学研究杂志(电子版), 2026, 20(05): 383-388.

Xiaoyi Wang, Zheyi Sun, Lijun Huo. Research progress on stem cell spheroids in the field of dental pulp regeneration[J/OL]. Chinese Journal of Stomatological Research(Electronic Edition), 2026, 20(05): 383-388.

牙髓及根尖周病是口腔多发病,但目前临床常用治疗方法均存在一定局限。牙髓功能性再生逐步成为口腔医学研究的重点与热点,其中干细胞移植技术尤为重要。相较于单细胞移植,干细胞微球可提升移植后细胞存活率;同时,与二维培养相比,微球能更精准地模拟体内微环境,维持干细胞更优异的生物学特性,在组织再生中展现出巨大潜力。本文系统概述干细胞微球的结构、形成机制和影响因素,重点总结其在牙髓再生领域的研究进展,分析现存挑战与发展方向,为其后续基础研究与临床转化提供参考。

Pulp and periapical diseases are prevalent conditions in dentistry, yet current clinical treatment approaches all exhibit certain limitations. Functional regeneration of dental pulp has progressively become a focal point and hot topic in oral medicine research, with stem cell transplantation technology being particularly significant. Compared to single-cell transplantation, stem cell spheroids can enhance post-transplantation cell survival rates; simultaneously, compared to two-dimensional culture, spheroids more accurately mimic the in vivo microenvironment, maintaining superior biological properties of stem cells and demonstrating significant potential in tissue regeneration. This article systematically reviews the structure, formation mechanism, and influencing factors of stem cell spheroids, with a particular emphasis on summarizing research progress in the field of pulp regeneration. It analyses existing challenges and future directions, providing a reference for subsequent basic research and clinical translation.

图1 细胞微球示意图
表1 干细胞微球在牙髓再生中的临床前研究总结
文献 干细胞来源 微球制备方法 动物模型 主要结果 局限性
Dissanayaka等[33] DPSC + HUVEC 微孔阵列法 免疫缺陷小鼠皮下移植 形成血管化牙髓样组织,可见类成牙本质细胞 缺乏功能性牙根发育的长期观察
Zhang等[34] DPSC 静电微滴法 裸鼠皮下移植 促牙髓样组织再生及新微血管形成 长期血管稳定性待验证,生物安全性未评估
Liang等[35] DPSC + HUVEC GelMA纤维载体 裸鼠皮下移植 生成牙髓样组织、血管及成牙本质样细胞 是否适用于临床根管注射未验证
Li等[36] DPSC、SHED 微孔阵列法 裸鼠皮下移植 通过Zn2+激活PI3K-AKT通路促血管生成 纳米材料长期生物安全性需评估
Yuan等[37] SHED 低黏附培养板 裸鼠皮下移植 适度生理性缺氧平衡活力与促血管能力 最佳尺寸可能因细胞类型而异
Jian等[38] DPSC 低黏附培养板 裸鼠皮下移植 促进血管化和神经标志物表达 未证实功能性神经支配
Ding等[39] SHED 低黏附培养板 裸鼠皮下移植 有效促进牙髓牙本质样组织的再生 RNA-seq结果并未阐明具体信号通路
Duan等[40] HERS 基质胶辅助法 大鼠肾囊下/皮下移植 矿化增强 移植后新生组织来源未明确
Griffin等[41] 胚胎牙细胞 悬滴法 免疫正常小鼠皮下移植 形成完整牙齿结构 细胞来源伦理及未形成完整的、功能性牙周膜附着
  PDLSC + HUVEC 微孔芯片法 大鼠上颌第一磨牙牙周缺损模型 促进牙骨质形成 未评估牙周膜质量、功能附着及长期稳定
  皮质骨来源MSC 低黏附培养板 免疫缺陷小鼠皮下移植 促进牙槽嵴新骨形成 机械强度及长期骨重塑效果有待验证
[1]
Lee H N,Liang C,Liao L,et al. Advances in research on stem cell-based pulp regeneration[J]. Tissue Eng Regen Med,2021,18(6):931-940. DOI:10.1007/s13770-021-00389-2.
[2]
Peng C,Zhao Y,Wang W,et al. Histologic findings of a human immature revascularized/regenerated tooth with symptomatic irreversible pulpitis[J]. J Endod,2017,43(6):905-909. DOI:10.1016/j.joen.2017.01.031.
[3]
欧乾民,李政诗,牛露菡,等.口腔干细胞的生物学特性与转化研究[J].北京大学学报(医学版),2025,57(5):827-835. DOI:10.19723/j.issn.1671-167X.2025.05.003.
[4]
Shi X,Hu X,Jiang N,et al. Regenerative endodontic therapy:From laboratory bench to clinical practice[J]. J Adv Res,2025(72):229-263. DOI:10.1016/j.jare.2024.07.001.
[5]
Xuan K,Li B,Guo H,et al. Deciduous autologous tooth stem cells regenerate dental pulp after implantation into injured teeth [J]. Sci Transl Med,2018,10(455):eaaf3227. DOI:10.1126/scitranslmed.aaf3227.
[6]
Huang X,Li Z,Liu A,et al. Microenvironment influences odontogenic mesenchymal stem cells mediated dental pulp regeneration[J]. Front Physiol,2021(12):656588. DOI:10.3389/fphys.2021.656588.
[7]
Ohori-Morita Y,Ashry A,Niibe K,et al. Current perspectives on the dynamic culture of mesenchymal stromal/stem cell spheroids[J]. Stem Cells Transl Med,2025,14(3):szae093. DOI:10.1093/stcltm/szae093.
[8]
Xu Q,Zhang C,Liu X,et al. Modulation of stem cell survival and engraftment:Implications for stem cell-based therapy[J]. Theranostics,2025,15(17):8840-8856. DOI:10.7150/thno.120805.
[9]
Jeong T,Lee M S,Jeon J,et al. Advanced stem cell therapy using both cell spheroids transplant and paracrine factor release hydrogel patches for myocardial infarction[J]. Colloids Surf B Biointerfaces,2025(253):114772. DOI:10.1016/j.colsurfb.2025.114772.
[10]
Liu Y,Zhang Y,Mei T,et al. hESCs-derived early vascular cell spheroids for cardiac tissue vascular engineering and myocardial infarction treatment[J]. Adv Sci(Weinh),2022,9(9):e2104299. DOI:10.1002/advs.202104299.
[11]
Liu X,Astudillo Potes M D,Dashtdar B,et al. 3D stem cell spheroids with 2D hetero-nanostructures for in vivo osteogenic and immunologic modulated bone repair[J]. Adv Healthc Mater,2024,13(12):e2303772. DOI:10.1002/adhm.202303772.
[12]
Ohori-Morita Y,Niibe K,Limraksasin P,et al. Novel mesenchymal stem cell spheroids with enhanced stem cell characteristics and bone regeneration ability[J]. Stem Cells Transl Med,2022,11(4):434-449. DOI:10.1093/stcltm/szab030.
[13]
Bi W,Cai S,Xing C,et al. Engineering mesenchymal stem cell spheroids and brain organoids:Advanced 3D culture platforms for neurodegenerative disease cell therapy[J]. Stem Cell Rev Rep,2026,22(4):1739-1763. DOI:10.1007/s12015-026-11101-z.
[14]
Gouveia Z,Özkan A,Giannobile W V,et al. Oral tissue spheroid,organoid,and organ-on chip microphysiological modeling strategies towards enhanced emulation of health and disease[J]. Bioeng Transl Med,2025,10(5):e70020. DOI:10.1002/btm2.70020.
[15]
Kang S M,Kim D,Lee J H,et al. Engineered microsystems for spheroid and organoid studies[J]. Adv Healthc Mater,2021,10(2):e2001284. DOI:10.1002/adhm.202001284.
[16]
Kim W,Gwon Y,Park S,et al. Therapeutic strategies of three-dimensional stem cell spheroids and organoids for tissue repair and regeneration[J]. Bioact Mater,2023(19):50-74. DOI:10.1016/j.bioactmat.2022.03.039.
[17]
Moro L G,Guarnier L P,Azevedo M F,et al. A brief history of cell culture:From harrison to organs-on-a-chip[J]. Cells,2024,13(24):2068. DOI:10.3390/cells13242068.
[18]
Garreta E,Kamm R D,Chuva de Sousa Lopes S M,et al. Rethinking organoid technology through bioengineering[J]. Nat Mater,2021,20(2):145-155. DOI:10.1038/s41563-020-00804-4.
[19]
Li Z,Hui J,Yang P,et al. Microfluidic organ-on-a-chip system for disease modeling and drug development[J]. Biosensors (Basel),2022,12(6):370. DOI:10.3390/bios12060370.
[20]
Fang Y,Eglen R M. Three-dimensional cell cultures in drug discovery and development[J]. SLAS Discov,2017,22(5):456-472. DOI:10.1177/2472555218787198.
[21]
Haraszti R A,Miller R,Stoppato M,et al. Exosomes produced from 3D cultures of MSCs by tangential flow filtration show higher yield and improved activity[J]. Mol Ther,2018,26(12):2838-2847. DOI:10.1016/j.ymthe.2018.09.015.
[22]
Ryu N E,Lee S H,Park H. Spheroid culture system methods and applications for mesenchymal stem cells[J]. Cells,2019,8(12):1620. DOI:10.3390/cells8121620.
[23]
Wadman M. FDA no longer has to require animal testing for new drugs[J]. Science,2023,379(6628):127-128. DOI:10.1126/science.adg6276.
[24]
Sart S,Tsai A C,Li Y,et al. Three-dimensional aggregates of mesenchymal stem cells:Cellular mechanisms,biological properties,and applications[J]. Tissue Eng Part B Rev,2014,20(5):365-380. DOI:10.1089/ten.TEB.2013.0537.
[25]
Fuentes P,Torres M J,Arancibia R,et al. Dynamic culture of mesenchymal stromal/stem cell spheroids and secretion of paracrine factors[J]. Front Bioeng Biotechnol,2022(10):916229. DOI:10.3389/fbioe.2022.916229.
[26]
Schmitz C,Potekhina E,Irianto T,et al. Hypoxia onset in mesenchymal stem cell spheroids:Monitoring with hypoxia reporter cells[J]. Front Bioeng Biotechnol,2021(9):611837. DOI:10.3389/fbioe.2021.611837
[27]
Shi W,Kwon J,Huang Y,et al. Facile tumor spheroids formation in large quantity with controllable size and high uniformity[J]. Sci Rep,2018,8(1):6837. DOI:10.1038/s41598-018-25203-3.
[28]
Shrestha S,Lekkala V K R,Acharya P,et al. Recent advances in microarray 3D bioprinting for high-throughput spheroid and tissue culture and analysis[J]. Essays Biochem,2021,65(3):481-489. DOI:10.1042/EBC20200150.
[29]
Tevlek A,Kecili S,Ozcelik O S,et al. Spheroid engineering in microfluidic devices[J]. ACS Omega,2023,8(4):3630-3649. DOI:10.1021/acsomega.2c06052.
[30]
Mohd N,Razali M,Ghazali M J,et al. Current advances of three-dimensional bioprinting application in dentistry:A scoping review [J]. Materials(Basel),2022,15(18):6398. DOI:10.3390/ma15186398.
[31]
Chae S,Hong J,Hwangbo H,et al. The utility of biomedical scaffolds laden with spheroids in various tissue engineering applications[J]. Theranostics,2021,11(14):6818-6832. DOI:10.7150/thno.58421.
[32]
Caprio N D,Burdick J A. Engineered biomaterials to guide spheroid formation,function,and fabrication into 3D tissue constructs[J]. Acta Biomater,2023(165):4-18. DOI:10.1016/j.actbio.2022.09.052.
[33]
Dissanayaka W L,Zhu L,Hargreaves K M,et al. Scaffold-free prevascularized microtissue spheroids for pulp regeneration[J]. J Dent Res,2014,93(12):1296-3103. DOI:10.1177/0022034514550040.
[34]
Zhang R,Xie L,Wu H,et al. Alginate/laponite hydrogel microspheres co-encapsulating dental pulp stem cells and VEGF for endodontic regeneration[J]. Acta Biomater,2020(113):305-316. DOI:10.1016/j.actbio.2020.07.012.
[35]
Liang Q,Liang C,Liu X,et al. Vascularized dental pulp regeneration using cell-laden microfiber aggregates[J]. J Mater Chem B,2022,10(48):10097-10111. DOI:10.1039/d2tb01825j.
[36]
Li Z,Wan M,Cui D,et al. DNMTi@ZIF-8 enhances biomimetic pulp regeneration via epigenetic regulation[J]. J Dent Res,2025,104(7):743-752. DOI:10.1177/00220345251315468.
[37]
Yuan X,Wang S,Yuan Z,et al. Boosting the angiogenesis potential of self-assembled mesenchymal stem cell spheroids by size mediated physiological hypoxia for vascularized pulp regeneration[J]. Acta Biomater,2025(198):102-114. DOI:10.1016/j.actbio.2025.04.019.
[38]
Jian W,Ma F,Xian Y,et al. Dental pulp stem cell-derived multicellular microtissue spheres:A synergistic strategy for dental pulp regeneration[J]. Int Dent J,2025,75(6):103970. DOI:10.1016/j.identj.2025.103970.
[39]
Ding J,Sun Z,Ma L,et al. Microspheres of stem cells from human exfoliated deciduous teeth exhibit superior pulp regeneration capacity[J]. Dent Mater,2025,41(1):70-80. DOI:10.1016/j.dental.2024.10.015.
[40]
Duan Y,Li X,Zhang S,et al. Therapeutic potential of HERS spheroids in tooth regeneration[J]. Theranostics,2020,10(16):7409-7421. DOI:10.7150/thno.44782.
[41]
Griffin K H,Fok S W,Kent Leach J. Strategies to capitalize on cell spheroid therapeutic potential for tissue repair and disease modeling[J]. NPJ Regen Med,2022,7(1):70. DOI:10.1038/s41536-022-00266-z.
[42]
Decarli M C,de Castro M V,Nogueira J A,et al. Development of a device useful to reproducibly produce large quantities of viable and uniform stem cell spheroids with controlled diameters [J]. Mater Sci Eng C Mater Biol Appl,2022(135):112685. DOI:10.1016/j.msec.2022.112685.
[43]
Cui X,Hartanto Y,Zhang H. Advances in multicellular spheroids formation[J]. J R Soc Interface,2017,14(127):20160877. DOI:10.1098/rsif.2016.0877.
[44]
Lee N H,Bayaraa O,Zechu Z,et al. Biomaterials-assisted spheroid engineering for regenerative therapy[J]. BMB Rep,2021,54(7):356-367. DOI:10.5483/BMBRep.2021.54.7.059.
[45]
Lu H,Li Y,Yang X,et al. Mechanical forces from intercellular peptide self-assembly drive spheroid formation[J]. Nat Commun,2026,17(1):1801. DOI:10.1038/s41467-026-68513-1.
[46]
Alsehli H S,Roy E,Williams T,et al. Morphogen-driven differentiation is precluded by physical confinement in human iPSCs spheroids[J]. Front Bioeng Biotechnol,2024(12):1467412. DOI:10.3389/fbioe.2024.
[1] 罗怡欣, 王泳翕, 谢晓云, 黎珂睿, 李杰, 张哲, 陈卓, 王芳. 不同分子分型乳腺癌类器官模型的构建与优化[J/OL]. 中华乳腺病杂志(电子版), 2026, 20(05): 318-322.
[2] 张传凯, 曾梦, 向凯, 任明星, 杨生. 刺激响应性生物材料在组织修复与再生中的微环境调控策略[J/OL]. 中华口腔医学研究杂志(电子版), 2026, 20(04): 262-272.
[3] 张文青, 强茹月, 裴丹丹, 张辉. 不同杨氏模量聚丙烯酰胺水凝胶模型的构建及其对小鼠骨髓间充质干细胞行为的影响[J/OL]. 中华口腔医学研究杂志(电子版), 2026, 20(04): 304-310.
[4] 许成裘, 李亮, 严聪. 疝与腹壁外科修补材料的发展:从人工假体到组织工程支架[J/OL]. 中华疝和腹壁外科杂志(电子版), 2026, 20(04): 477-480.
[5] 李文芳, 董孟炜, 杨万彭, 巴特, 南楠, 刘杨, 郝慧琴. 关节腔注射脂肪间充质干细胞对碘乙酸钠诱导大鼠急性软骨损伤的抗炎及组织学修复作用[J/OL]. 中华细胞与干细胞杂志(电子版), 2026, 16(05): 266-277.
[6] 成津, 郭建明. 间充质干细胞治疗糖尿病足溃疡的研究现状与进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2026, 16(05): 278-284.
[7] 郑宏, 孙碧红, 苑倩, 杨培, 刘阳. 毛囊干细胞的研究进展与应用探索[J/OL]. 中华细胞与干细胞杂志(电子版), 2026, 16(05): 285-291.
[8] 姚雪, 曹佩琪, 杨林花. 造血干细胞移植在骨髓增生异常综合征治疗中的研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2026, 16(05): 292-297.
[9] 王琼, 刘媛, 巩婷, 刘奕晞, 谭震, 但刚, 胡丽娜, 郭郑斌, 张睿. 高原低氧诱导红细胞增多的细胞机制研究进展及干细胞治疗潜力[J/OL]. 中华细胞与干细胞杂志(电子版), 2026, 16(05): 298-304.
[10] 陈博扬, 孔垂玉, 周庆. 多系分化应激耐受细胞在组织损伤修复中的研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2026, 16(05): 305-313.
[11] 谢乐静, 顾新新, 郝秀雪. 干细胞治疗老年糖尿病的作用机制及临床研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2026, 16(05): 314-320.
[12] 刘丽丽, 高笑微, 张志华. 大块组织块法分离培养人脐带间充质干细胞的可行性研究[J/OL]. 中华细胞与干细胞杂志(电子版), 2026, 16(04): 193-200.
[13] 闫鸣琪, 向秋玲. 诱导多能干细胞分化的心肌细胞在遗传性原发性心律失常综合征模型中的研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2026, 16(04): 233-239.
[14] 赵娟, 田峻. 脂肪源性间充质干细胞向骨髓腔归巢促进骨组织修复的研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2026, 16(04): 240-245.
[15] 刘欣贤, 陈柏煜, 魏玲玲. 细胞治疗糖尿病的临床突破与进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2026, 16(04): 246-254.
阅读次数
全文


摘要


AI
小
编
AI小编
你好!我是《中华医学电子期刊资源库》AI小编,有什么可以帮您的吗?