Extracellular Vesicles Delivering Nuclear Factor I/C for Hard Tissue Engineering: Treatment of Apical Periodontitis and Dentin Regeneration

Overview

Journal J Tissue Eng

Date 2022 Mar 24

PMID 35321254

Authors

Shengyan Yang

Qing Liu

Shijing Chen

Fuping Zhang

Yaoyin Li

Wenguo Fan

Lijia Mai

Hongwen He

Fang Huang

Affiliations

Soon will be listed here.

Abstract

Apical periodontitis (AP) causes arrest of tooth root development, which is associated with impaired odontoblastic differentiation of stem cells from apical papilla (SCAPs), but the underlying mechanism remains unclear. Here, we investigated roles of extracellular vesicle (EV) in AP and odontoblastic differentiation of SCAPs, moreover, a novel nuclear factor I/C (NFIC)-encapsulated EV was developed to promote dentin regeneration. We detected a higher expression of EV marker CD63 in inflamed apical papilla, and found that EVs from LPS-stimulated dental pulp cells suppressed odontoblastic differentiation of SCAPs through downregulating NFIC. Furthermore, we successfully constructed the NFIC-encapsulated EV by overexpressing NFIC in HEK293FT cells, which could upregulate cellular NFIC level in SCAPs, promoting the proliferation and migration of SCAPs, as well as dentinogenesis both in vitro and in vivo. Collectively, based on pathological roles of EV in AP, our study provides a novel strategy for dentin regeneration by exploiting EV to deliver NFIC.

Citing Articles

Emerging roles of extracellular vesicles in oral and maxillofacial areas.

Wang Q, Sun J, Jiang H, Yu M Int J Oral Sci. 2025; 17(1):11.

PMID: 39900916 PMC: 11791077. DOI: 10.1038/s41368-024-00341-9.

Synthetic Vesicle-Based Drug Delivery Systems for Oral Disease Therapy: Current Applications and Future Directions.

Huang P, Li W, Guan J, Jia Y, Wang D, Chen Y J Funct Biomater. 2025; 16(1).

PMID: 39852581 PMC: 11766321. DOI: 10.3390/jfb16010025.

Histological Evaluation of Sodium Iodide-Based Root Canal Filling Materials in Canine Teeth.

Lee J, Lee S, Park H, Kim Y, Lee H, Han M Materials (Basel). 2025; 17(24.

PMID: 39769682 PMC: 11727976. DOI: 10.3390/ma17246082.

3D culture inhibits replicative senescence of SCAPs via UQCRC2-mediated mitochondrial oxidative phosphorylation.

Shi Y, Xiao T, Weng Y, Xiao Y, Wu J, Wang J J Transl Med. 2024; 22(1):1129.

PMID: 39707408 PMC: 11662480. DOI: 10.1186/s12967-024-05953-7.

Extracellular vesicles as therapeutic tools in regenerative dentistry.

Xia E, Zou S, Zhao X, Liu W, Zhang Y, Zhao I Stem Cell Res Ther. 2024; 15(1):365.

PMID: 39402576 PMC: 11476107. DOI: 10.1186/s13287-024-03936-5.

References

Zhuang X, Ji L, Jiang H, Liu Y, Liu X, Bi J . Exosomes Derived from Stem Cells from the Apical Papilla Promote Dentine-Pulp Complex Regeneration by Inducing Specific Dentinogenesis. Stem Cells Int. 2020; 2020:5816723. PMC: 7273441. DOI: 10.1155/2020/5816723. View

Nagelkerke A, Ojansivu M, van der Koog L, Whittaker T, Cunnane E, Silva A . Extracellular vesicles for tissue repair and regeneration: Evidence, challenges and opportunities. Adv Drug Deliv Rev. 2021; 175:113775. DOI: 10.1016/j.addr.2021.04.013. View

Kalluri R, LeBleu V . The biology function and biomedical applications of exosomes. Science. 2020; 367(6478). PMC: 7717626. DOI: 10.1126/science.aau6977. View

Zhang J, Wang Z, Jiang Y, Niu Z, Fu L, Luo Z . Nuclear Factor I-C promotes proliferation and differentiation of apical papilla-derived human stem cells in vitro. Exp Cell Res. 2015; 332(2):259-66. DOI: 10.1016/j.yexcr.2015.01.020. View

Shi W, Guo S, Liu L, Liu Q, Huo F, Ding Y . Small Extracellular Vesicles from Lipopolysaccharide-Preconditioned Dental Follicle Cells Promote Periodontal Regeneration in an Inflammatory Microenvironment. ACS Biomater Sci Eng. 2020; 6(10):5797-5810. DOI: 10.1021/acsbiomaterials.0c00882. View

Sun J, Shen H, Shao L, Teng X, Chen Y, Liu X . HIF-1α overexpression in mesenchymal stem cell-derived exosomes mediates cardioprotection in myocardial infarction by enhanced angiogenesis. Stem Cell Res Ther. 2020; 11(1):373. PMC: 7455909. DOI: 10.1186/s13287-020-01881-7. View

Wang D, Lyu Y, Yang Y, Zhang S, Chen G, Pan J . Schwann cell-derived EVs facilitate dental pulp regeneration through endogenous stem cell recruitment via SDF-1/CXCR4 axis. Acta Biomater. 2021; 140:610-624. DOI: 10.1016/j.actbio.2021.11.039. View

Tsiapalis D, ODriscoll L . Mesenchymal Stem Cell Derived Extracellular Vesicles for Tissue Engineering and Regenerative Medicine Applications. Cells. 2020; 9(4). PMC: 7226943. DOI: 10.3390/cells9040991. View

Hargreaves K, Diogenes A, Teixeira F . Treatment options: biological basis of regenerative endodontic procedures. J Endod. 2013; 39(3 Suppl):S30-43. PMC: 3589799. DOI: 10.1016/j.joen.2012.11.025. View

10.

Lv L, Feng Y, Wu M, Wang B, Li Z, Zhong X . Exosomal miRNA-19b-3p of tubular epithelial cells promotes M1 macrophage activation in kidney injury. Cell Death Differ. 2019; 27(1):210-226. PMC: 7206053. DOI: 10.1038/s41418-019-0349-y. View

11.

Lin Y, Wu J, Gu W, Huang Y, Tong Z, Huang L . Exosome-Liposome Hybrid Nanoparticles Deliver CRISPR/Cas9 System in MSCs. Adv Sci (Weinh). 2018; 5(4):1700611. PMC: 5908366. DOI: 10.1002/advs.201700611. View

12.

Xu C, Xie X, Zhao L, Wu Y, Wang J . The critical role of nuclear factor I-C in tooth development. Oral Dis. 2021; 28(8):2093-2099. DOI: 10.1111/odi.14046. View

13.

Lin Y, Nan J, Shen J, Lv X, Chen X, Lu X . Canagliflozin impairs blood reperfusion of ischaemic lower limb partially by inhibiting the retention and paracrine function of bone marrow derived mesenchymal stem cells. EBioMedicine. 2020; 52:102637. PMC: 6992997. DOI: 10.1016/j.ebiom.2020.102637. View

14.

Li J, Wang B, Kodali M, Chen C, Kim E, Patters B . In vivo evidence for the contribution of peripheral circulating inflammatory exosomes to neuroinflammation. J Neuroinflammation. 2018; 15(1):8. PMC: 5759808. DOI: 10.1186/s12974-017-1038-8. View

15.

Perez P, Romaniuk M, Duette G, Zhao Z, Huang Y, Martin-Jaular L . Extracellular vesicles and chronic inflammation during HIV infection. J Extracell Vesicles. 2020; 8(1):1687275. PMC: 6963413. DOI: 10.1080/20013078.2019.1687275. View

16.

Roh S, Park J . The role of nuclear factor I-C in tooth and bone development. J Korean Assoc Oral Maxillofac Surg. 2017; 43(2):63-69. PMC: 5410429. DOI: 10.5125/jkaoms.2017.43.2.63. View

17.

Zhang J, Zhang Y, Lv H, Yu Q, Zhou Z, Zhu Q . Human stem cells from the apical papilla response to bacterial lipopolysaccharide exposure and anti-inflammatory effects of nuclear factor I C. J Endod. 2013; 39(11):1416-22. DOI: 10.1016/j.joen.2013.07.018. View

18.

Zhou C, Yang G, Chen M, Wang C, He L, Xiang L . Lhx8 mediated Wnt and TGFβ pathways in tooth development and regeneration. Biomaterials. 2015; 63:35-46. PMC: 4583713. DOI: 10.1016/j.biomaterials.2015.06.004. View

19.

Jin Q, Li P, Yuan K, Zhao F, Zhu X, Zhang P . Extracellular vesicles derived from human dental pulp stem cells promote osteogenesis of adipose-derived stem cells via the MAPK pathway. J Tissue Eng. 2020; 11:2041731420975569. PMC: 7716067. DOI: 10.1177/2041731420975569. View

20.

Tavasolian F, Moghaddam A, Rohani F, Abdollahi E, Janzamin E, Momtazi-Borojeni A . Exosomes: Effectual players in rheumatoid arthritis. Autoimmun Rev. 2020; 19(6):102511. DOI: 10.1016/j.autrev.2020.102511. View