Restorative Dentistry and Endodontics

The Korean Academy of Conservative Dentistry (대한치과보존학회)
권호 표지
DOI QR코드

DOI QR Code

Stem cell-derived exosomes for dentin-pulp complex regeneration: a mini-review

  • Dina A. Hammouda (Department of Oral Biology, Faculty of Dentistry, Mansoura University) ;
  • Alaa M Mansour (Department of Oral Biology, Faculty of Dentistry, Mansoura University) ;
  • Mahmoud A. Saeed (Department of Oral Biology, Faculty of Dentistry, Menoufia University) ;
  • Ahmed R. Zaher (Department of Oral Biology, Faculty of Dentistry, Mansoura University) ;
  • Mohammed E. Grawish (Department of Oral Biology, Faculty of Dentistry, Mansoura University)
  • Received : 2023.01.29
  • Accepted : 2023.03.22
  • Published : 2023.05.31
Download PDF
⟨ Previous Next ⟩

Abstract

This mini-review was conducted to present an overview of the use of exosomes in regenerating the dentin-pulp complex (DPC). The PubMed and Scopus databases were searched for relevant articles published between January 1, 2013 and January 1, 2023. The findings of basic in vitro studies indicated that exosomes enhance the proliferation and migration of mesenchymal cells, as human dental pulp stem cells, via mitogen-activated protein kinases and Wingless-Int signaling pathways. In addition, they possess proangiogenic potential and contribute to neovascularization and capillary tube formation by promoting endothelial cell proliferation and migration of human umbilical vein endothelial cells. Likewise, they regulate the migration and differentiation of Schwann cells, facilitate the conversion of M1 pro-inflammatory macrophages to M2 anti-inflammatory phenotypes, and mediate immune suppression as they promote regulatory T cell conversion. Basic in vivo studies have indicated that exosomes triggered the regeneration of dentin-pulp-like tissue, and exosomes isolated under odontogenic circumstances are particularly strong inducers of tissue regeneration and stem cell differentiation. Exosomes are a promising regenerative tool for DPC in cases of small pulp exposure or for whole-pulp tissue regeneration.

Keywords

References

  1. Yu C, Abbott PV. An overview of the dental pulp: its functions and responses to injury. Aust Dent J 2007;52 Supplement:S4-S16. https://doi.org/10.1111/j.1834-7819.2007.tb06111.x
  2. Goldberg M, Kulkarni AB, Young M, Boskey A. Dentin: structure, composition and mineralization. Front Biosci (Elite Ed) 2011;3:711-735. https://doi.org/10.2741/e281
  3. Cordeiro MM, Dong Z, Kaneko T, Zhang Z, Miyazawa M, Shi S, Smith AJ, Nor JE. Dental pulp tissue engineering with stem cells from exfoliated deciduous teeth. J Endod 2008;34:962-969. https://doi.org/10.1016/j.joen.2008.04.009
  4. Duncan HF, Yamauchi Y. Pulp exposure management. Clin Dent Rev 2019;3:4.
  5. Swanson WB, Gong T, Zhang Z, Eberle M, Niemann D, Dong R, Rambhia KJ, Ma PX. Controlled release of odontogenic exosomes from a biodegradable vehicle mediates dentinogenesis as a novel biomimetic pulp capping therapy. J Control Release 2020;324:679-694. https://doi.org/10.1016/j.jconrel.2020.06.006
  6. Huang CC, Narayanan R, Alapati S, Ravindran S. Exosomes as biomimetic tools for stem cell differentiation: applications in dental pulp tissue regeneration. Biomaterials 2016;111:103-115. https://doi.org/10.1016/j.biomaterials.2016.09.029
  7. Li Z, Liu L, Wang L, Song D. The effects and potential applications of concentrated growth factor in dentin-pulp complex regeneration. Stem Cell Res Ther 2021;12:357.
  8. Simon SR, Berdal A, Cooper PR, Lumley PJ, Tomson PL, Smith AJ. Dentin-pulp complex regeneration: from lab to clinic. Adv Dent Res 2011;23:340-345. https://doi.org/10.1177/0022034511405327
  9. Asgary S, Parirokh M, Eghbal MJ, Ghoddusi J. SEM evaluation of pulp reaction to different pulp capping materials in dog's teeth. Iran Endod J 2006;1:117-123.
  10. Aljandan B, AlHassan H, Saghah A, Rasheed M, Ali AA. The effectiveness of using different pulp-capping agents on the healing response of the pulp. Indian J Dent Res 2012;23:633-637. https://doi.org/10.4103/0970-9290.107381
  11. Boland GM, Perkins G, Hall DJ, Tuan RS. Wnt 3a promotes proliferation and suppresses osteogenic differentiation of adult human mesenchymal stem cells. J Cell Biochem 2004;93:1210-1230. https://doi.org/10.1002/jcb.20284
  12. Giuroiu CL, Caruntu ID, Lozneanu L, Melian A, Vataman M, Andrian S. Dental pulp: correspondences and contradictions between clinical and histological diagnosis. BioMed Res Int 2015;2015:960321.
  13. Imura N, Pinheiro ET, Gomes BP, Zaia AA, Ferraz CC, Souza-Filho FJ. The outcome of endodontic treatment: a retrospective study of 2000 cases performed by a specialist. J Endod 2007;33:1278-1282. https://doi.org/10.1016/j.joen.2007.07.018
  14. Cvek M. Prognosis of luxated non-vital maxillary incisors treated with calcium hydroxide and filled with gutta-percha. A retrospective clinical study. Endod Dent Traumatol 1992;8:45-55. https://doi.org/10.1111/j.1600-9657.1992.tb00228.x
  15. Kim JY, Xin X, Moioli EK, Chung J, Lee CH, Chen M, Fu SY, Koch PD, Mao JJ. Regeneration of dental-pulp-like tissue by chemotaxis-induced cell homing. Tissue Eng Part A 2010;16:3023-3031. https://doi.org/10.1089/ten.tea.2010.0181
  16. Garcia-Godoy F, Murray PE. Recommendations for using regenerative endodontic procedures in permanent immature traumatized teeth. Dent Traumatol 2012;28:33-41. https://doi.org/10.1111/j.1600-9657.2011.01044.x
  17. Palma PJ, Ramos JC, Martins JB, Diogenes A, Figueiredo MH, Ferreira P, Viegas C, Santos JM. Histologic evaluation of regenerative endodontic procedures with the use of chitosan scaffolds in immature dog teeth with apical periodontitis. J Endod 2017;43:1279-1287. https://doi.org/10.1016/j.joen.2017.03.005
  18. Palma PJ, Martins J, Diogo P, Sequeira D, Ramos JC, Diogenes A, Sequeira D, Ramos JC, Diogenes A, Santos JM. Does apical papilla survive and develop in apical periodontitis presence after regenerative endodontic procedures? Appl Sci 2019;9:3942-3955. https://doi.org/10.3390/app9193942
  19. Chrepa V, Pitcher B, Henry MA, Diogenes A. Survival of the apical papilla and its resident stem cells in a case of advanced pulpal necrosis and apical periodontitis. J Endod 2017;43:561-567. https://doi.org/10.1016/j.joen.2016.09.024
  20. Smith AJ, Cassidy N, Perry H, Begue-Kirn C, Ruch JV, Lesot H. Reactionary dentinogenesis. Int J Dev Biol 1995;39:273-280. https://doi.org/10.1016/0003-9969(94)90029-9
  21. Simon S, Smith AJ, Berdal A, Lumley PJ, Cooper PR. The MAP kinase pathway is involved in odontoblast stimulation via p38 phosphorylation. J Endod 2010;36:256-259. https://doi.org/10.1016/j.joen.2009.09.019
  22. Bai Y, Cheng X, Liu X, Guo Q, Wang Z, Fu Y, He W, Yu Q. Transforming growth factor-β1 promotes early odontoblastic differentiation of dental pulp stem cells via activating AKT, Erk1/2 and p38 MAPK pathways. J Dent Sci 2023;18:87-94. https://doi.org/10.1016/j.jds.2022.06.027
  23. Guo W, Fan Z, Wang S, Du J. ALK5 is essential for tooth germ differentiation during tooth development. Biotech Histochem 2019;94:481-490. https://doi.org/10.1080/10520295.2018.1552018
  24. Nakashima M, Iohara K. Mobilized dental pulp stem cells for pulp regeneration: initiation of clinical trial. J Endod 2014;40 Supplement:S26-S32. https://doi.org/10.1016/j.joen.2014.01.020
  25. Nakashima M, Iohara K, Murakami M, Nakamura H, Sato Y, Ariji Y, Matsushita K. Pulp regeneration by transplantation of dental pulp stem cells in pulpitis: a pilot clinical study. Stem Cell Res Ther 2017;8:61.
  26. Mitsiadis TA, Orsini G, Jimenez-Rojo L. Stem cell-based approaches in dentistry. Eur Cell Mater 2015;30:248-257. https://doi.org/10.22203/eCM.v030a17
  27. Nassar W, El-Ansary M, Sabry D, Mostafa MA, Fayad T, Kotb E, Temraz M, Saad AN, Essa W, Adel H. Umbilical cord mesenchymal stem cells derived extracellular vesicles can safely ameliorate the progression of chronic kidney diseases. Biomater Res 2016;20:21.
  28. Ivica A, Ghayor C, Zehnder M, Valdec S, Weber FE. Pulp-derived exosomes in a fibrin-based regenerative root filling material. J Clin Med 2020;9:491.
  29. Cooper LF, Ravindran S, Huang CC, Kang M. A role for exosomes in craniofacial tissue engineering and regeneration. Front Physiol 2020;10:1569. 
  30. Xian X, Gong Q, Li C, Guo B, Jiang H. Exosomes with highly angiogenic potential for possible use in pulp regeneration. J Endod 2018;44:751-758. https://doi.org/10.1016/j.joen.2017.12.024
  31. Hu X, Zhong Y, Kong Y, Chen Y, Feng J, Zheng J. Lineage-specific exosomes promote the odontogenic differentiation of human dental pulp stem cells (DPSCs) through TGFβ1/smads signaling pathway via transfer of microRNAs. Stem Cell Res Ther 2019;10:170.
  32. Zhang S, Thiebes AL, Kreimendahl F, Ruetten S, Buhl EM, Wolf M, Jockenhoevel S, Apel C. Extracellular vesicles-loaded fibrin gel supports rapid neovascularization for dental pulp regeneration. Int J Mol Sci 2020;21:4226.
  33. Zhang S, Yang Y, Jia S, Chen H, Duan Y, Li X, Wang S, Wang T, Lyu Y, Chen G, Tian W. Exosome-like vesicles derived from Hertwig's epithelial root sheath cells promote the regeneration of dentin-pulp tissue. Theranostics 2020;10:5914-5931. https://doi.org/10.7150/thno.43156
  34. Zhuang X, Ji L, Jiang H, Liu Y, Liu X, Bi J, Zhao W, Ding Z, Chen X. Exosomes derived from stem cells from the apical papilla promote dentine-pulp complex regeneration by inducing specific dentinogenesis. Stem Cells Int 2020;2020:5816723.
  35. Huang X, Qiu W, Pan Y, Li J, Chen Z, Zhang K, Luo Y, Wu B, Xu W. Exosomes from LPS-stimulated hDPSCs activated the angiogenic potential of HUVECs in vitro. Stem Cells Int 2021;2021:6685307.
  36. Chen WJ, Xie J, Lin X, Ou MH, Zhou J, Wei XL, Chen WX. The role of small extracellular vesicles derived from lipopolysaccharide-preconditioned human dental pulp stem cells in dental pulp regeneration. J Endod 2021;47:961-969. https://doi.org/10.1016/j.joen.2021.03.010
  37. Wu M, Liu X, Li Z, Huang X, Guo H, Guo X, Yang X, Li B, Xuan K, Jin Y. SHED aggregate exosomes shuttled miR-26a promote angiogenesis in pulp regeneration via TGF-β/SMAD2/3 signalling. Cell Prolif 2021;54:e13074.
  38. Li J, Ju Y, Liu S, Fu Y, Zhao S. Exosomes derived from lipopolysaccharide-preconditioned human dental pulp stem cells regulate Schwann cell migration and differentiation. Connect Tissue Res 2021;62:277-286. https://doi.org/10.1080/03008207.2019.1694010
  39. Zeng J, He K, Mai R, Lin T, Wei R, Nong J, Wu Y. Exosomes from human umbilical cord mesenchymal stem cells and human dental pulp stem cells ameliorate lipopolysaccharide-induced inflammation in human dental pulp stem cells. Arch Oral Biol 2022;138:105411.
  40. Yu S, Chen X, Liu Y, Zhuang XY, Wang AC, Liu XM, Zhu S. Exosomes derived from stem cells from the apical papilla alleviate inflammation in rat pulpitis by upregulating regulatory T cells. Int Endod J 2022;55:517-530. https://doi.org/10.1111/iej.13721
  41. Stanko P, Altanerova U, Jakubechova J, Repiska V, Altaner C. Dental mesenchymal stem/stromal cells and their exosomes. Stem Cells Int 2018;2018:8973613.
  42. Thery C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol 2002;2:569-579. https://doi.org/10.1038/nri855
  43. Fevrier B, Raposo G. Exosomes: endosomal-derived vesicles shipping extracellular messages. Curr Opin Cell Biol 2004;16:415-421. https://doi.org/10.1016/j.ceb.2004.06.003
  44. Qian X, An N, Ren Y, Yang C, Zhang X, Li L. Immunosuppressive effects of mesenchymal stem cells-derived exosomes. Stem Cell Rev Rep 2021;17:411-427. https://doi.org/10.1007/s12015-020-10040-7
  45. Zara M, Amadio P, Campodonico J, Sandrini L, Barbieri SS. Exosomes in cardiovascular diseases. Diagnostics (Basel) 2020;10:943.
  46. Guo SC, Tao SC, Yin WJ, Qi X, Yuan T, Zhang CQ. Exosomes derived from platelet-rich plasma promote the re-epithelization of chronic cutaneous wounds via activation of YAP in a diabetic rat model. Theranostics 2017;7:81-96.  https://doi.org/10.7150/thno.16803
  47. Brunello G, Zanotti F, Trentini M, Zanolla I, Pishavar E, Favero V, Favero R, Favero L, Bressan E, Bonora M, Sivolella S, Zavan B. Exosomes derived from dental pulp stem cells show different angiogenic and osteogenic properties in relation to the age of the donor. Pharmaceutics 2022;14:908.