The Role of Mesenchymal Stem Cells in Dentistry: A Review

Abstract

Mesenchymal stem cells (MSCs) have garnered significant attention in regenerative dentistry due to their remarkable ability to differentiate into various cell types and their immunomodulatory properties. This review provides a comprehensive overview of recent advancements in MSC research relevant to dentistry, focusing on their potential applications in periodontal tissue regeneration, dental pulp regeneration, and maxillofacial bone repair. Periodontal diseases, which affect the tissues surrounding and supporting the teeth, are a significant challenge in dentistry. Current treatments often involve surgical intervention and tissue grafting. MSCs have shown promise as a potential alternative for periodontal tissue regeneration, as they can differentiate into periodontal ligament cells, cementoblasts, and osteoblasts. Several preclinical and clinical studies have demonstrated the efficacy of MSC-based therapies in periodontal regeneration. Dental pulp regeneration is another area where MSCs hold promise. Damaged or infected dental pulp can lead to pulpitis or pulp necrosis, necessitating root canal treatment. MSCs have been studied for their ability to regenerate dental pulp tissue and promote pulp healing. They can differentiate into odontoblast-like cells and regenerate dentin-like tissue, making them a potential treatment option for dental pulp regeneration. In maxillofacial bone repair, MSCs have been investigated for their osteogenic differentiation potential and ability to stimulate bone regeneration. Studies have shown promising results, suggesting that MSC-based therapies could be a viable treatment option for maxillofacial bone defects. The mechanisms underlying MSC-based therapies in dentistry are not fully understood but are thought to involve a combination of paracrine effects, immunomodulation, and differentiation into specific cell types. Future research should focus on addressing these challenges and exploring novel approaches for enhancing the regenerative potential of MSCs in dentistry.

Keywords:

mesenchymal stem cells, regenerative dentistry, periodontal tissue regeneration, dental pulp regeneration, maxillofacial bone repair, immunomodulation, tissue engineering, stem cell therapy

References
[1] Hu L, Yin C, Zhao F, Ali A, Ma J, Qian A. Mesenchymal stem cells: Cell fate decision to osteoblast or adipocyte and application in osteoporosis treatment. Int J Mol Sci. 2018 Jan;19(2):360.

[2] Poblano-Pérez LI, Castro-Manrreza ME, González- Alva P, Fajardo-Orduña GR, Montesinos JJ. Mesenchymal stromal cells derived from dental tissues: Immunomodulatory properties and clinical potential [Internet]. Int J Mol Sci. 2024 Feb;25(4):1986.

[3] Lin H, Chen H, Zhao X, Chen Z, Zhang P, Tian Y, et al. Advances in mesenchymal stem cell conditioned medium-mediated periodontal tissue regeneration. J Transl Med. 2021 Nov;19(1):456.

[4] Dave JR, Tomar GB. Dental tissue-derived mesenchymal stem cells: Applications in tissue engineering. Crit Rev Biomed Eng. 2018;46(5):429–468.

[5] Sramkó B, Földes A, Kádár K, Varga G, Zsembery Á, Pircs K. The wisdom in teeth: Neuronal differentiation of dental pulp cells. Cell Reprogram. 2023 Feb;25(1):32–44.

[6] Kruminis-Kaszkiel E, Osowski A, Bejer-Oleńska E, Dziekoński M, Wojtkiewicz J. Differentiation of human mesenchymal stem cells from Wharton’s Jelly towards neural stem cells using a feasible and repeatable protocol. Cells. 2020 Mar;9(3):739.

[7] Pisciotta A, Bertoni L, Vallarola A, Bertani G, Mecugni D, Carnevale G. Neural crest derived stem cells from dental pulp and tooth-associated stem cells for peripheral nerve regeneration. Neural Regen Res. 2020 Mar;15(3):373–381.

[8] Yuan SM, Yang XT, Zhang SY, Tian WD, Yang B. Therapeutic potential of dental pulp stem cells and their derivatives: Insights from basic research toward clinical applications. World J Stem Cells. 2022 Jul;14(7):435–452.

[9] Roth DM, Bayona F, Baddam P, Graf D. Craniofacial development: Neural crest in molecular embryology. Head Neck Pathol. 2021 Mar;15(1):1–15.

[10] Yang D, Solidum JG, Park D. Dental pulp stem cells and current in vivo approaches to study dental pulp stem cells in pulp injury and regeneration. J Bone Metab. 2023 Aug;30(3):231–244.

[11] Luo L, He Y, Wang X, Key B, Lee BH, Li H, et al. Potential roles of dental pulp stem cells in neural regeneration and repair. Stem Cells Int. 2018;(2018):1731289. https://doi.org/10.1155/2018/1731289

[12] Yang X, Li L, Xiao L, Zhang D. Recycle the dental fairy’s package: Overview of dental pulp stem cells. Stem Cell Res Ther. 2018 Dec;9(1):347.

[13] Ogata K, Moriyama M, Matsumura-Kawashima M, Kawado T, Yano A, Nakamura S. The therapeutic potential of secreted factors from dental pulp stem cells for various diseases. Biomedicines. 2022 May;10(5):1049.

[14] He P, Zhang Q, Motiwala FI, Shanti RM, Chang BM, Le AD. Potential application of dental stem cells in regenerative reconstruction of oral and maxillofacial tissues: A narrative review. Front Oral Maxillofac Med. 2022 Jun;4:14.

[15] Yang B, Qiu Y, Zhou N, Ouyang H, Ding J, Cheng B, et al. Application of stem cells in oral disease therapy: Progresses and perspectives. Front Physiol. 2017 Apr;8:197.

[16] Regmi S, Pathak S, Kim JO, Yong CS, Jeong JH. Mesenchymal stem cell therapy for the treatment of inflammatory diseases: Challenges, opportunities, and future perspectives. Eur J Cell Biol. 2019 Dec;98(5-8):151041.

[17] Soudi A, Yazdanian M, Ranjbar R, Tebyanian H, Yazdanian A, Tahmasebi E, et al. Role and application of stem cells in dental regeneration: A comprehensive overview. EXCLI J. 2021 Feb;20:454–489.

[18] Bhuyan R, Bhuyan SK, Mohanty JN, Das S, Juliana N, Juliana IF. Periodontitis and its inflammatory changes linked to various systemic diseases: A review of its underlying mechanisms [Internet]. Biomedicines. 2022 Oct;10(10):2659.

[19] Rinčić G, Gaćina P, Virović Jukić L, Rinčić N, Božić D, Badovinac A. Association between periodontitis and liver disease. Acta Clin Croat. 2022 Feb;60(3):510– 518.

[20] Deas DE, Moritz AJ, Sagun RS Jr, Gruwell SF, Powell CA. Scaling and root planing vs. conservative surgery in the treatment of chronic periodontitis. Periodontol 2000. 2016 Jun;71(1):128–139.

[21] Okić-Đorđević I, Obradović H, Kukolj T, Petrović A, Mojsilović S, Bugarski D, et al. Dental mesenchymal stromal/stem cells in different microenvironmentsimplications in regenerative therapy. World J Stem Cells. 2021 Dec;13(12):1863–1880.

[22] Amato M, Santonocito S, Viglianisi G, Tatullo M, Isola G. Impact of oral mesenchymal stem cells applications as a promising therapeutic target in the therapy of periodontal disease. Int J Mol Sci. 2022 Nov;23(21):13419.

[23] Nguyen-Thi TD, Nguyen-Huynh BH, Vo-Hoang TT, Nguyen-Thanh T. Stem cell therapies for periodontal tissue regeneration: A meta-analysis of clinical trials. J Oral Biol Craniofac Res. 2023;13(5):589–597.

[24] Smojver I, Katalinić I, Bjelica R, Gabrić D, Matišić V, Molnar V, et al. Mesenchymal stem cells based treatment in dental medicine: A narrative review. Int J Mol Sci. 2022 Jan;23(3):1662.

[25] Shabbir J, Farooq I, Ali S, Mohammed F, Bugshan A, Khurram SA, et al. Dental pulp. An illustrated guide to oral histology. 2021;69-79. https://doi.org/10.1002/9781119669616.ch5

[26] Farges JC, Alliot-Licht B, Renard E, Ducret M, Gaudin A, Smith AJ, et al. Dental pulp defence and repair mechanisms in dental caries. Mediators Inflamm. 2015;(2015):230251. https://doi.org/10.1155/2015/230251

[27] Sabeti M, Ghobrial D, Zanjir M, da Costa BR, Young Y, Azarpazhooh A. Treatment outcomes of regenerative endodontic therapy in immature permanent teeth with pulpal necrosis: A systematic review and network meta-analysis [doi]. Int Endod J. 2024 Mar;57(3):238–255.

[28] Kwack KH, Lee HW. Clinical potential of dental pulp stem cells in pulp regeneration: Current endodontic progress and future perspectives. Front Cell Dev Biol. 2022 Apr;10:857066.

[29] Singh RK, Shakya VK, Khanna R, Singh BP, Jindal G, Kirubakaran R, et al. Interventions for managing immature permanent teeth with necrotic pulps [doi]. Cochrane Libr. 2017;2017.

[30] Huang GT, Gronthos S, Shi S. Mesenchymal stem cells derived from dental tissues vs. those from other sources: Their biology and role in regenerative medicine. J Dent Res. 2009 Sep;88(9):792–806.

[31] Ledesma-Martinez E, Mendoza-Nunez VM, Santiago-Osorio E. Mesenchymal stem cells derived from dental pulp: A review. Stem Cells Int. 2016;(2016):4709572. https://doi.org/10.1155/2016/4709572

[32] Koh B, Sulaiman N, Ismadi SN, Ramli R, Yunus SS, Idrus RB, et al. Mesenchymal stem cells: A comprehensive methods for odontoblastic induction. Biol Proced Online. 2021 Sep;23(1):18.

[33] Rehman A, Nigam A, Laino L, Russo D, Todisco C, Esposito G, et al. Mesenchymal stem cells in soft tissue regenerative medicine: A comprehensive review. Medicina (Kaunas). 2023 Aug;59(8):1449.

[34] Lee HN, Liang C, Liao L, Tian WD. Advances in research on stem cell-based pulp regeneration. Tissue Eng Regen Med. 2021 Dec;18(6):931–940.

[35] Akhlaghi N, Khademi A. Outcomes of vital pulp therapy in permanent teeth with different medicaments based on review of the literature. Dent Res J (Isfahan). 2015;12(5):406–417.

[36] Lim HK, Choi YJ, Choi WC, Song IS, Lee UL. Reconstruction of maxillofacial bone defects using patient-specific long-lasting titanium implants. Sci Rep. 2022 May;12(1):7538.

[37] Hofer SO, Payne CE. Functional and aesthetic outcome enhancement of head and neck reconstruction through secondary procedures. Semin Plast Surg. 2010 Aug;24(3):309–318.

[38] Ferraz MP. Bone grafts in dental medicine: An overview of autografts, allografts and synthetic materials. Materials (Basel). 2023 May;16(11):4117.

[39] Stamnitz S, Klimczak A. Mesenchymal stem cells, bioactive factors, and scaffolds in bone repair: From research perspectives to clinical practice. Cells. 2021 Jul;10(8):1925.

[40] Costela-Ruiz VJ, Melguizo-Rodríguez L, Bellotti C, Illescas-Montes R, Stanco D, Arciola CR, et al. Different sources of mesenchymal stem cells for tissue regeneration: A guide to identifying the most favorable one in orthopedics and dentistry applications. Int J Mol Sci. 2022 Jun;23(11):6356.

[41] Re F, Borsani E, Rezzani R, Sartore L, Russo D. Bone regeneration using mesenchymal stromal cells and biocompatible scaffolds: A concise review of the current clinical trials. Gels. 2023 May;9(5):389.

[42] Bowles-Welch AC, Jimenez AC, Stevens HY, Frey Rubio DA, Kippner LE, Yeago C, et al. Mesenchymal stromal cells for bone trauma, defects, and disease: Considerations for manufacturing, clinical translation, and effective treatments. Bone Rep. 2023 Jan;18:101656.

[43] Andrukhov O, Behm C, Blufstein A, Rausch-Fan X. Immunomodulatory properties of dental tissuederived mesenchymal stem cells: Implication in disease and tissue regeneration. World J Stem Cells. 2019 Sep;11(9):604–617.

[44] Han Y, Yang J, Fang J, Zhou Y, Candi E, Wang J, et al. The secretion profile of mesenchymal stem cells and potential applications in treating human diseases. Signal Transduct Target Ther. 2022 Mar;7(1):92.

[45] Alvites R, Branquinho M, Sousa AC, Lopes B, Sousa P, Maurício AC. Mesenchymal stem/stromal cells and their paracrine activity-immunomodulation mechanisms and how to influence the therapeutic potential. Pharmaceutics. 2022 Feb;14(2):381.

[46] Song N, Scholtemeijer M, Shah K. Mesenchymal stem cell immunomodulation: Mechanisms and therapeutic potential. Trends Pharmacol Sci. 2020 Sep;41(9):653–664.

[47] Li X, Guan Y, Li C, Zhang T, Meng F, Zhang J, et al. Immunomodulatory effects of mesenchymal stem cells in peripheral nerve injury. Stem Cell Res Ther. 2022 Jan;13(1):18.

[48] Li B, Ouchi T, Cao Y, Zhao Z, Men Y. Dental-derived mesenchymal stem cells: State of the art. Front Cell Dev Biol. 2021 Jun;9:654559.

[49] Hade MD, Suire CN, Suo Z. Mesenchymal stem cell-derived exosomes: Applications in regenerative medicine. Cells. 2021 Aug;10(8):1959.

[50] Liang T, Chen L, Liu X, Li Y, Li Z, Yang D, et al. The role of extracellular vesicles in the development of nasopharyngeal carcinoma and potential clinical applications. Cancer Med. 2023 Jul;12(13):14484– 14497.

[51] Yu B, Zhang X, Li X. Exosomes derived from mesenchymal stem cells. Int J Mol Sci. 2014Mar;15(3):4142–4157.

[52] Dabrowska S, Andrzejewska A, Janowski M, Lukomska B. Immunomodulatory and regenerative effects of mesenchymal stem cells and extracellular vesicles: Therapeutic outlook for inflammatory and degenerative diseases. Front Immunol. 2021 Feb;11:591065.

[53] Fan XL, Zhang Y, Li X, Fu QL. Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy. Cell Mol Life Sci. 2020 Jul;77(14):2771–2794.

[54] Kandeel M, Morsy MA, Alkhodair KM, Alhojaily S. Mesenchymal stem cell-derived extracellular vesicles: An emerging diagnostic and therapeutic biomolecules for neurodegenerative disabilities. Biomolecules. 2023 Aug;13(8):1250.

[55] Aly RM. Current state of stem cell-based therapies: An overview. Stem Cell Investig. 2020 May;7:8.

[56] Yang JW, Shin YY, Seo Y, Kim HS. Therapeutic functions of stem cells from oral cavity: an update. Int J Mol Sci. 2020 Jun;21(12):4389.

[57] Kim DW, Jeong HS, Kim E, Lee H, Choi CH, Lee SJ. Oral delivery of stem-cell-loaded hydrogel microcapsules restores gut inflammation and microbiota. J Control Release. 2022 Jul;347:508–520.

[58] Wu J, Li G, Ye T, Lu G, Li R, Deng L, et al. Stem cell-laden injectable hydrogel microspheres for cancellous bone regeneration. Chem Eng J. 2020;393:124715.

[59] Yamada Y, Nakamura-Yamada S, Kusano K, Baba S. Clinical potential and current progress of dental pulp stem cells for various systemic diseases in regenerative medicine: A concise review. Int J Mol Sci. 2019 Mar;20(5):1132.

[60] Zhou LL, Liu W, Wu YM, Sun WL, Dörfer CE, Fawzy El-Sayed KM. Oral mesenchymal stem/progenitor cells: The immunomodulatory masters. Stem Cells Int. 2020;(2020):1327405. https://doi.org/10.1155/2020/1327405

[61] Zakrzewski W, Dobrzynski M, Rybak Z, Szymonowicz M, Wiglusz RJ. Selected nanomaterials’ application enhanced with the use of stem cells in acceleration of alveolar bone regeneration during augmentation process. Nanomaterials (Basel). 2020 Jun;10(6):1216.

[62] Niklason LE. Understanding the extracellular matrix to enhance stem cell-based tissue regeneration. Cell Stem Cell. 2018 Mar;22(3):302–305.

[63] Xiong Y, Tang R, Xu J, Jiang W, Gong Z, Zhang L, et al. Sequential transplantation of exosomes and mesenchymal stem cells pretreated with a combination of hypoxia and Tongxinluo efficiently facilitates cardiac repair [doi]. Stem Cell Res Ther. 2022 Feb;13(1):63.