Published: 2022-01-28

The role of stem cell therapy in endodontics and its future

Mohammad Khaled Aljifan, Abdulrhman Ali Alshuwayi, Abdulaziz Saeed Almatrafi, Abdulelah Mohammed Shukr, Khalid Abdullah Alshahrani, Abdullah Abdulelah Almuhanna, Mohammed Abdullah AlMuhanna, Khalid Nasser Alshammari, Ahmed Abdullah Alghamdi, Mazen Dhafer Albahri, Muath Muhammad Benten


Regenerative therapy has been introduced in the literature for a long time and is currently being practiced in different fields, including dentistry and endodontics. Many applications have been reported in the literature for stem cell therapy. However, many complications and adverse events were reported in this context. The present literature review sheds more light on the clinical applications of stem cell therapy in regenerative endodontics and the future perspectives in this field. There are no doubts that there are many questions to be answered despite the huge advances in this field. In response to tissue injury, it has been shown that stem cell therapy can strengthen the efficacy of physiological response to these events and improve tissue regeneration. They can be used for managing cases of reversible pulpitis. Moreover, evidence indicates that they can enhance the revascularization of necrotic pulp tissues. Accordingly, these outcomes can significantly change the perspectives of clinical endodontic practice, and current root canal management modalities and perhaps draws researchers into discovering further future applications for other currently untreatable conditions. However, further future investigations are still needed to understand more about the mechanisms of these modalities and improve their clinical applicability.



Stem cell, Regenerative therapy, Endodontics, Root canal treatment

Full Text:



Salehrabi R, Rotstein I. Endodontic treatment outcomes in a large patient population in the USA: an epidemiological study. J Endodontics. 2004;30(12):846-50.

Lazarski MP, Walker WA, 3rd, Flores CM, Schindler WG, Hargreaves KM. Epidemiological evaluation of the outcomes of nonsurgical root canal treatment in a large cohort of insured dental patients. J Endodontics. 2001;27(12):791-6.

Friedman S, Mor C. The success of endodontic therapy-healing and functionality. J Calif Dental Asso. 2004;32(6):493-503.

Malhotra N, Mala K. Regenerative endodontics as a tissue engineering approach: past, current and future. Aus Endodontic J. 2012;38(3):137-48.

Bansal R, Bansal R. Regenerative endodontics: a state of the art. Indian J Dental Res. 2011;22(1):122-31.

Son PT, Reda A, Viet DC. Exchange transfusion in the management of critical pertussis in young infants: a case series. Vox Sang. 2021;116(9):976-82.

Banchs F, Trope M. Revascularization of immature permanent teeth with apical periodontitis: new treatment protocol? J Endodontics. 2004;30(4):196-200.

Iwaya SI, Ikawa M, Kubota M. Revascularization of an immature permanent tooth with apical periodontitis and sinus tract. Dental Traumatol. 2001;17(4):185-7.

Rule DC, Winter GB. Root growth and apical repair subsequent to pulpal necrosis in children. Bri Dental J. 1966;120(12):586-90.

Hans MK, Shetty S. Regenerative endodontics: a paradigm shift in dental practice. Indian journal of dental research : official publication of Indian Society for Dental Research. 2009;20(4):517-518.

Ulloa-Montoya F, Verfaillie CM, Hu WS. Culture systems for pluripotent stem cells. J Biosci Bioengineering. 2005;100(1):12-27.

Garcia-Godoy F, Murray PE. Recommendations for using regenerative endodontic procedures in permanent immature traumatized teeth. Dental Traumatol. 2012;28(1):33-41.

Kindler V. Postnatal stem cell survival: does the niche, a rare harbor where to resist the ebb tide of differentiation, also provide lineage-specific instructions? J Leukocyte Biol. 2005;78(4):836-44.

Nakashima M, Akamine A. The application of tissue engineering to regeneration of pulp and dentin in endodontics. J Endodontics. 2005;31(10):711-8.

Brazelton TR, Blau HM. Optimizing techniques for tracking transplanted stem cells in vivo. Stem cells (Dayton, Ohio). 2005;23(9):1251-65.

Balic A, Aguila HL, Caimano MJ, Francone VP, Mina M. Characterization of stem and progenitor cells in the dental pulp of erupted and unerupted murine molars. Bone. 2010;46(6):1639-51.

Shi S, Gronthos S. Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp. J Bone Mineral Res. 2003;18(4):696-704.

El-Qushayri AE, Dahy A, Reda A. A closer look at the high burden of psychiatric disorders among healthcare workers in Egypt during the COVID-19 pandemic. Epidemiol Health. 2021;43:e2021045.

Miura M, Gronthos S, Zhao M. SHED: stem cells from human exfoliated deciduous teeth. Proceedings National Academy Sci US Am. 2003;100(10):5807-12.

Nakamura S, Yamada Y, Katagiri W, Sugito T, Ito K, Ueda M. Stem cell proliferation pathways comparison between human exfoliated deciduous teeth and dental pulp stem cells by gene expression profile from promising dental pulp. J Endodontics. 2009;35(11):1536-42.

Koyama N, Okubo Y, Nakao K, Bessho K. Evaluation of pluripotency in human dental pulp cells. J Oral Maxillofac Surg. 2009;67(3):501-6.

Gronthos S, Brahim J, Li W. Stem cell properties of human dental pulp stem cells. J Dental Res. 2002;81(8):531-5.

Huang GT, Yamaza T, Shea LD. Stem/progenitor cell-mediated de novo regeneration of dental pulp with newly deposited continuous layer of dentin in an in vivo model. Tissue engineering Part A. 2010;16(2):605-15.

Sakai VT, Zhang Z, Dong Z. SHED differentiate into functional odontoblasts and endothelium. J Dental Res. 2010;89(8):791-6.

Linde A, Goldberg M. Dentinogenesis. Crit Reviews Oral Biol Med. 1993;4(5):679-728.

Ruch JV, Lesot H, Bègue-Kirn C. Odontoblast differentiation. The International journal of developmental biology. 1995;39(1):51-68.

Kramer IR. The vascular architecture of the human dental pulp. Arch Oral Biol. 1960;2:177-89.

Goldberg M, Kulkarni AB, Young M, Boskey A. Dentin: structure, composition and mineralization. Frontiers in bioscience (Elite edition). 2011;3:711-35.

Takahashi K. Pulpal vascular changes in inflammation. Proceedings Finnish Dental Society Suomen Hammaslaakariseuran toimituksia. 1992;88(1):381-5.

Smith AJ, Cassidy N, Perry H, Bègue-Kirn C, Ruch JV, Lesot H. Reactionary dentinogenesis. Int J Dev Biol. 1995;39(1):273-80.

Linde A, Lundgren T. From serum to the mineral phase. The role of the odontoblast in calcium transport and mineral formation. Int J Developmental Biol. 1995;39(1):213-22.

Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9(6):669-76.

Nör JE, Christensen J, Mooney DJ, Polverini PJ. Vascular endothelial growth factor (VEGF)-mediated angiogenesis is associated with enhanced endothelial cell survival and induction of Bcl-2 expression. Am J Pathol. 1999;154(2):375-84.

Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science. 1989;246(4935):1306-9.

Botero TM, Son JS, Vodopyanov D, Hasegawa M, Shelburne CE, Nör JE. MAPK signaling is required for LPS-induced VEGF in pulp stem cells. J Dental Res. 2010;89(3):264-9.

Botero TM, Mantellini MG, Song W, Hanks CT, Nör JE. Effect of lipopolysaccharides on vascular endothelial growth factor expression in mouse pulp cells and macrophages. Eur J Oral Sci. 2003;111(3):228-34.

Telles PD, Hanks CT, Machado MA, Nör JE. Lipoteichoic acid up-regulates VEGF expression in macrophages and pulp cells. J Dental Res. 2003;82(6):466-70.

Güven G, Altun C, Günhan O. Co-expression of cyclooxygenase-2 and vascular endothelial growth factor in inflamed human pulp: an immunohistochemical study. J Endodontics. 2007;33(1):18-20.

Ikeda E, Morita R, Nakao K. Fully functional bioengineered tooth replacement as an organ replacement therapy. Proceedings National Academy Sci U S Am. 2009;106(32):13475-80.

Nguyen TM, Huan VT, Reda A. Clinical features and outcomes of neonatal dengue at the Children's Hospital 1, Ho Chi Minh, Vietnam. J Clin Virol. 2021;138:104758.

Thieu H, Bach Dat B, Nam NH. Antibiotic resistance of Helicobacter pylori infection in a children's hospital in Vietnam: prevalence and associated factors. Minerva Medica. 2020;111(5):498-501.

Kumar M, Varma K, Satish R, Nanduri Mk, Raju S, Rao M. Stem cells in endodontic therapy. Int J Med Res Health Sci. 2014;3:977.

Bakhtiar H, Mazidi SA, Mohammadi Asl S. The role of stem cell therapy in regeneration of dentine-pulp complex: a systematic review. Progress Biomaterials. 2018;7(4):249-68.