THE USE OF STEM CELLS IN PERIODONTAL REGENERATION
Abstract
Periodontitis is defined as a chronic infectious-inflammatory disease associated with a dysbiotic biofilm, leading to an imbalance in homeostasis, the loss of periodontal supporting tissues, and potentially culminating in tooth loss. The frequent occurrence of periodontal bone defects has driven growing interest in dentistry in periodontal regeneration, involving the constant search for new biomaterials and, more recently, the introduction of stem cell-based therapies. The aim of this literature review is to analyze the therapeutic potential of mesenchymal stem cells (MSCs) in periodontal regeneration, addressing the challenges associated with their clinical application. Mesenchymal stem cells, particularly derived from the periodontal ligament, have shown significant potential in regenerating damaged periodontal tissues. Studies indicate that these cells have the ability to differentiate into various cell types, including osteoblasts, cementoblasts, and fibroblasts, which are essential for the formation of new periodontal tissue.
Author Biographies
Univeritas UNG.
Univeritas UNG.
Univeritas UNG.
Graduated in Dentistry (1997), Master's degree (2001), and Ph.D. (2003) in Dental Clinic - concentration area in Operative Dentistry from FOP UNICAMP, Proficiency in Laser by the Academy of Laser Dentistry ALD-USA. Research Professor in the Graduate Program and Undergraduate Dentistry at Universidade Guarulhos - UNG. Professor in the Dentistry course at Universidade São Judas Tadeu - USJT. Faculty Associate in the Dentistry/Restorative Dental Sciences department at the Health Science Center of the University of Florida. Has experience in Dental Clinic in the field of Operative Dentistry, conducting research on teeth whitening, composite resins, and dental caries. Email: gutojar@yahoo.com
Univeritas UNG.
References
AGGARWAL, S.; PITTENGER, M. F. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood, v. 105, p. 1815–22, 2005 DOI: https://doi.org/10.1182/blood-2004-04-1559 DOI: https://doi.org/10.1182/blood-2004-04-1559
ARCURI, L.J.; ABUD, L. G.; DUARTE, F. P. et al. Haploidentical transplantation with post-transplant cyclophosphamide versus unrelated donor hematopoietic stem cell transplantation: A systematic review and meta-analysis. Biol Blood Marrow Transplant, v. 25, n. 12, p. 2422–30, 2019 DOI: https://doi.org/10.1016/j.bbmt.2019.08.018 DOI: https://doi.org/10.1016/j.bbmt.2019.07.028
CAI, X.; YANG, F.; WALBOOMERS, X. F. et al. Periodontal regeneration via chemoattractive constructs. J Clin Periodontol., v. 45, p. 851–60, 2018 DOI: https://doi.org/10.1111/jcpe.12935 DOI: https://doi.org/10.1111/jcpe.12928
CHEN, F. M.; GAO, L. N.; TIAN, B. M. et al. Treatment of periodontal intrabony defects using autologous periodontal ligament stem cells: a randomized clinical trial. Stem Cell Res Ther, v. 7, p. 33, 2016 DOI: https://doi.org/10.1186/s13287-016-0296-8 DOI: https://doi.org/10.1186/s13287-016-0288-1
CHEN, F. M.; SUN, H. H.; LU, H. et al. Stem cell-delivery therapeutics for periodontal tissue regeneration. Biomaterials, v. 33, p. 6320–44, 2012 DOI: https://doi.org/10.1016/j.biomaterials.2012.05.048 DOI: https://doi.org/10.1016/j.biomaterials.2012.05.048
CHEN, Y.; LIU, H. O potencial de diferenciação de células-tronco mesenquimais gengivais induzidas por meio condicionado de células germinativas dentais apicais. Mol Med Rep., v. 14, p. 3565–72, 2016 DOI: https://doi.org/10.3892/mmr.2016.5690 DOI: https://doi.org/10.3892/mmr.2016.5690
COSTA, L. A.; EIRO, N.; VACA, A.; VIZOSO, F. J. Towards a new concept of regenerative endodontics based on mesenchymal stem cell-derived secretome products. Bioengineering (Basel)., v. 10, n. 1, p. 4, 2022 DOI: https://doi.org/10.3390/bioengineering10010004 DOI: https://doi.org/10.3390/bioengineering10010004
CROSSMAN, J.; ELYASI, M.; EL-BIALY, T.; FLORES-MIR, C. Cementum regeneration using stem cells in the dog model: A systematic review. Arch Oral Biol., v. 91, p. 78–90, 2018 DOI: https://doi.org/10.1016/j.archoralbio.2018.03.015 DOI: https://doi.org/10.1016/j.archoralbio.2018.04.001
DE WERT, G.; MUMMERY, C. Human embryonic stem cells: Research, ethics and policy. Hum Reprod., v. 18, p. 672–82, 2003 DOI: https://doi.org/10.1093/humrep/deg143 DOI: https://doi.org/10.1093/humrep/deg143
DHOTE, R.; CHARDE, P.; BHONGADE, M.; RAO, J. Stem cells cultured on beta tricalcium phosphate (β-TCP) in combination with recombinant human platelet-derived growth factor-BB (rh-PDGF-BB) for the treatment of human infrabony defects. J Stem Cells., v. 10, p. 243–54, 2015.
DOGAN, A.; OZDEMIR, A.; KUBAR, A.; OYGUR, T. Assessment of periodontal healing by seeding of fibroblast-like cells derived from regenerated periodontal ligament in artificial furcation defects in a dog: a pilot study. Tissue Eng., v. 8, p. 273–82, 2002 DOI: https://doi.org/10.1089/107632702753725004 DOI: https://doi.org/10.1089/107632702753725030
DOSS, M. X.; SACHINIDIS, A. Current challenges of iPSC-based disease modeling and therapeutic implications. Cells, v. 8, 2019 DOI: https://doi.org/10.3390/cells8050403 DOI: https://doi.org/10.3390/cells8050403
FEI, X.; JIANG, S.; ZHANG, S. et al. Isolation, culture, and identification of amniotic fluid-derived mesenchymal stem cells. Cell Biochem Biophys, 67, p. 689–94, 2013 DOI: https://doi.org/10.1007/s12013-013-9564-5 DOI: https://doi.org/10.1007/s12013-013-9558-z
FERRAROTTI, F.; ROMANO, F.; GAMBA, M. N. et al. Human intrabony defect regeneration with micrografts containing dental pulp stem cells: A randomized controlled clinical trial. J Clin Periodontol., v. 45, p. 841–50, 2018 DOI: https://doi.org/10.1111/jcpe.12934 DOI: https://doi.org/10.1111/jcpe.12931
FU, X.; XU, Y. Challenges to the clinical application of pluripotent stem cells: Towards genomic and functional stability. Genome Med., v. 4, p. 55, 2012 DOI: https://doi.org/10.1186/gm367 DOI: https://doi.org/10.1186/gm354
GARTNER, S.; KAPLAN, H. S. Long-term culture of human bone marrow cells. Proc Natl Acad Sci U S A., v. 77, p. 4756–9, 1980 DOI: https://doi.org/10.1073/pnas.77.8.4756 DOI: https://doi.org/10.1073/pnas.77.8.4756
GOULD, T. R.; MELCHER, A. H.; BRUNETTE, D. M. Migration and division of progenitor cell populations in periodontal ligament after wounding. J Periodont Res., v. 15, p. 20–42, 1980 DOI: https://doi.org/10.1111/j.1600-0765.1980.tb00297.x DOI: https://doi.org/10.1111/j.1600-0765.1980.tb00258.x
GRONTHOS, S.; MANKANI, M.; BRAHIM, J.; ROBEY, P. G.; SHI, S. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci U S A., v. 97, p. 13625–30, 2000 DOI: https://doi.org/10.1073/pnas.240309797 DOI: https://doi.org/10.1073/pnas.240309797
HA, D. H.; KIM, H.; LEE, J. et al. Mesenchymal stem/stromal cell-derived exosomes for immunomodulatory therapeutics and skin regeneration. Cells, v. 9, 2020 DOI: https://doi.org/10.3390/cells9112240 DOI: https://doi.org/10.3390/cells9051157
HAN, J.; MENICANIN, D.; GRONTHOS, S. et al. Stem cells, tissue engineering and periodontal regeneration. Aust Dent J., v. 59, p. 117–30, 2014 DOI: https://doi.org/10.1111/adj.12114 DOI: https://doi.org/10.1111/adj.12100
HE, W.; GOODKIND, A. L.; KOWALECZKO, M. et al. Cancer treatment evolution from traditional methods to stem cells and gene therapy. Curr Gene Ther., v. 22, n. 5, p. 368–85, 2022 DOI: https://doi.org/10.2174/1566523222666220420124039 DOI: https://doi.org/10.2174/1566523221666211119110755
HERNÁNDEZ-MONJARAZ, B.; SANTIAGO-OSORIO, E.; LEDESMA-MARTÍNEZ, E. et al. Retrieval of a periodontally compromised tooth by allogeneic grafting of mesenchymal stem cells from dental pulp: A case report. J Int Med Res., v. 46, p. 2983–93, 2018 DOI: https://doi.org/10.1177/0300060518779070 DOI: https://doi.org/10.1177/0300060518773244
HUANG, G. T. J.; 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., v. 88, p. 792–806, 2009 DOI: https://doi.org/10.1177/0022034509340867 DOI: https://doi.org/10.1177/0022034509340867
IVANOVSKI, S.; VAQUETTE, C.; GRONTHOS, S. et al. Multiphasic scaffolds for periodontal tissue engineering. J Dent Res., v. 93, p. 1212–21, 2014 DOI: https://doi.org/10.1177/0022034514547278 DOI: https://doi.org/10.1177/0022034514544301
JIANG, J.; WU, X.; LIN, M. et al. Application of autologous periosteal cells for the regeneration of class III furcation defects in Beagle dogs. Cytotechnology., v. 62, p. 235–43, 2010 DOI: https://doi.org/10.1007/s10616-010-9262-y DOI: https://doi.org/10.1007/s10616-010-9284-y
KIM, S. G. A cell-based approach to dental pulp regeneration using mesenchymal stem cells: A scoping review. Int J Mol Sci., v. 22, n. 9, p. 4357, 2021 DOI: https://doi.org/10.3390/ijms22094357 DOI: https://doi.org/10.3390/ijms22094357
LEITE SEGUNDO, A. V.; VASCONCELOS, B. C. do E. Células-tronco e engenharia tecidual: perspectivas de aplicação em odontologia. Rev Ciências Médicas., v. 16, 2007.
LI, X.; HE, X. T.; YIN, Y. et al. Administration of signalling molecules dictates stem cell homing for in situ regeneration. J Cell Mol Med., v. 21, p. 3162–77, 2017 DOI: https://doi.org/10.1111/jcmm.13223 DOI: https://doi.org/10.1111/jcmm.13286
LØVSCHALL, H.; ARENHOLT-BINDSLEV, D.; CLAUSEN, P. P.; KARRING, T. Activation of the Notch signaling pathway in response to pulp capping of rat molars. Eur J Oral Sci, v. 113, n. 4, p. 312–7, 2005 DOI: https://doi.org/10.1111/j.1600-0722.2005.00221.x DOI: https://doi.org/10.1111/j.1600-0722.2005.00221.x
MIURA, M.; GRONTHOS, S.; ZHAO, M.; LU, B.; FISHER, L. W.; ROBEY, P. G.; SHI, S. SHED: Stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci USA., v. 100, n. 10, p. 5807–12, 2003 DOI: https://doi.org/10.1073/pnas.0937635100 DOI: https://doi.org/10.1073/pnas.0937635100
MROZIK, K. M.; WADA, N.; MARINO, V.; RICHTER, W.; SHI, S.; WHEELER, D. L.; GRONTHOS, S.; BARTOLD, P. M. Regeneration of periodontal tissues using allogeneic periodontal ligament stem cells in an ovine model. Regen Med., v. 8, n. 6, p. 711–23, 2013 DOI: https://doi.org/10.2217/rme.13.69 DOI: https://doi.org/10.2217/rme.13.66
NAGATA, M.; AKAMINE, Y.; KURASHINA, K. Meio condicionado de células-tronco do ligamento periodontal melhora a regeneração periodontal. Tissue Eng Part A., v. 23, n. 9–10, p. 367–77, 2017 DOI: https://doi.org/10.1089/ten.TEA.2016.0252
NÚÑEZ, J.; SANZ-BLASCO, S.; VIGNOLETTI, F.; VALLÉS, C.; FIGUERO, E.; SANZ, M. Periodontal regeneration: stem cells and platelet-rich plasma: from basic research to the clinic and future development of cell transplantation therapy for tissue regeneration. Int J Dent., v. 2012, p. 307024, 2012 DOI: https://doi.org/10.1155/2012/307024 DOI: https://doi.org/10.1155/2012/307024
PAPAPANOU, P. N.; SANZ, M.; BUDUNELI, N.; DIETRICH, T.; FERES, M.; FINE, D. H. et al. Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Clin Periodontol., v. 45, Suppl 20, S170, 2018 DOI: https://doi.org/10.1111/jcpe.12946 DOI: https://doi.org/10.1111/jcpe.12946
PARK, C. H.; KIM, K. H.; LEE, Y. M.; SEOL, Y. J. Advanced engineering strategies for periodontal complex regeneration. Materials (Basel), v. 9, n. 7, p. 57, 2016 DOI: https://doi.org/10.3390/ma907057 DOI: https://doi.org/10.3390/ma9010057
PARK, J. M.; KIM, J.; KIM, M. Y.; KIM, S. W. Effects of mesenchymal stem cell on dopaminergic neurons, motor and memory functions in animal models of Parkinson's disease: a systematic review and meta-analysis. Neural Regen Res., v. 19, n. 7, p. 1584–92, 2024 DOI: https://doi.org/10.4103/1673-5374.371482 DOI: https://doi.org/10.4103/1673-5374.387976
PENG, Y.; KE, M.; XUE, W.; NI, Y.; HE, C.; DENG, Z. Donor-derived mesenchymal stem cells combined with low-dose tacrolimus prevent acute rejection after renal transplantation: A clinical pilot study. Transplantation., v. 95, n. 2, p. 161–8, 2013 DOI: https://doi.org/10.1097/TP.0b013e318271caa2 DOI: https://doi.org/10.1097/TP.0b013e3182754c53
PIRES, I. G.; BATISTA, N. F.; RODRIGUES, R. C.; DE SOUZA, A. G.; MARTINS, A. V.; RODRIGUES, L. G. Clinical efficacy of stem-cell therapy on diabetes mellitus: A systematic review and meta-analysis. Transpl Immunol., v. 75, p. 101740, 2022 DOI: https://doi.org/10.1016/j.trim.2022.101740 DOI: https://doi.org/10.1016/j.trim.2022.101740
PREISIG, E.; SCHROEDER, H. E. Long‐term culture of human periodontal ligament cells with autologous root discs. J Periodontal Res., v. 23, n. 3, p. 211–6, 1988 DOI: https://doi.org/10.1111/j.1600-0765.1988.tb01547.x DOI: https://doi.org/10.1111/j.1600-0765.1988.tb01360.x
QIU, J.; ZHOU, J.; WANG, J.; CHEN, L.; TAN, J.; ZHENG, L. et al. Improvement of periodontal tissue regeneration by conditioned medium of mesenchymal stem cells derived from gingiva or periodontal ligament: a comparative study in rats. Stem Cell Res Ther., v. 11, n. 1, p. 42, 2020 DOI: https://doi.org/10.1186/s13287-020-1551-0 DOI: https://doi.org/10.1186/s13287-019-1546-9
QUINLAN, A. R.; BOLAND, M. J.; BALL, M. P.; MELTON, C.; VANDENBERG, D. J.; ILIFF, B. W. et al. Genome sequencing of mouse induced pluripotent stem cells reveals retroelement stability and infrequent DNA rearrangement during reprogramming. Cell Stem Cell., v. 9, n. 4, p. 366–73, 2011 DOI: https://doi.org/10.1016/j.stem.2011.09.008 DOI: https://doi.org/10.1016/j.stem.2011.07.018
ROMANOV, Y. A.; SVINTSITSKAYA, V. A.; SMIRNOV, V. N. Searching for alternative sources of postnatal human mesenchymal stem cells: Candidate MSC-like cells from umbilical cord. Stem Cells., v. 21, n. 1, p. 105–10, 2003 DOI: https://doi.org/10.1634/stemcells.21-1-105 DOI: https://doi.org/10.1634/stemcells.21-1-105
SALARI SEDIGH, H.; SAFFARPOUR, A.; JAMSHIDI, S.; ASHOURI, M.; NASSIRI, S. M.; DEHGHAN, M. M.; RANJBAR, E.; SHAFIEIAN, R. In vitro investigation of canine periodontal ligament-derived mesenchymal stem cells: A possibility of promising tool for periodontal regeneration. J Oral Biol Craniofac Res., v. 13, p. 403–411, 2023 DOI: https://doi.org/10.1016/j.jobcr.2023.02.005 DOI: https://doi.org/10.1016/j.jobcr.2023.03.010
SÁNCHEZ, N.; MATOS, S.; NUNES, R.; CARDOSO, J.; RIBEIRO, F.; MARTINS, T. Periodontal regeneration using a xenogeneic bone substitute seeded with autologous periodontal ligament-derived mesenchymal stem cells: A 12-month quasi-randomized controlled pilot clinical trial. J Clin Periodontol., v. 47, p. 1391–1402, 2020 DOI: https://doi.org/10.1111/jcpe.13382 DOI: https://doi.org/10.1111/jcpe.13368
SANTOS, N. C. C. D.; COTRIM, K. C.; ACHÔA, G. L.; KALIL, E. C.; KANTARCI, A.; BUENO, D. F. The use of mesenchymal stromal/stem cells (MSC) for periodontal and peri-implant regeneration: Scoping review. Braz Dent J., v. 25, p. 35, 2024. DOI: https://doi.org/10.1590/0103-6440202406134
SEO, B. M.; MIURA, M.; GRONTHOS, S.; BARTOLD, P. M.; BATOULI, S.; BRAHIM, J.; YOUNG, M.; GEHRON, R. P.; SHI, S. Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet., v. 364, p. 149–155, 2004 DOI: https://doi.org/10.1016/S0140-6736(04)16627-0 DOI: https://doi.org/10.1016/S0140-6736(04)16627-0
SHARKIS, S. J.; JONES, R. J.; CIVIN, C.; JANG, Y. Y. Pluripotent stem cell-based cancer therapy: Promise and challenges. Sci Transl Med, v. 4, p. 127ps9, 2012 DOI: https://doi.org/10.1126/scitranslmed.3003623 DOI: https://doi.org/10.1126/scitranslmed.3003920
TAKAHASHI, K.; TANABE, K.; OHNUKI, M.; NARITA, M.; ICHISAKA, T.; TOMODA, K.; YAMANAKA, S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell., v. 131, p. 861–872, 2007 DOI: https://doi.org/10.1016/j.cell.2007.11.019 DOI: https://doi.org/10.1016/j.cell.2007.11.019
TAKAHASHI, K.; YAMANAKA, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell., v. 126, p. 663–676, 2006 DOI: https://doi.org/10.1016/j.cell.2006.07.024 DOI: https://doi.org/10.1016/j.cell.2006.07.024
THESLEFF, I.; NIEMINEN, P. Tooth morphogenesis and cell differentiation. Curr Opin Cell Biol., v. 8, p. 844–850, 1996 DOI: https://doi.org/10.1016/S0955-0674(96)80133-3 DOI: https://doi.org/10.1016/S0955-0674(96)80086-X
TSUMANUMA, Y, IWATA, T, WASHIO, K, YOSHIDA, T, YAMADA, A, TAKAYAMA, S, TSUJI, Y.; SHIBATA, Y.; BABA, S.; ANDO, T.; YAMATO, M.; OKANO, T.; IZUMI, Y. Comparison of different tissue-derived stem cell sheets for periodontal regeneration in a canine 1-wall defect model. Biomaterials, v. 32, p. 5819–5825, 2011 DOI: https://doi.org/10.1016/j.biomaterials.2011.04.056 DOI: https://doi.org/10.1016/j.biomaterials.2011.04.071
UCCELLI, A.; MORETTA, L.; PISTOIA, V. Mesenchymal stem cells in health and disease. Nat Rev Immunol., v. 8, p. 726–736, 2008 DOI: https://doi.org/10.1038/nri2395 DOI: https://doi.org/10.1038/nri2395
WAGNER, J.; KEAN, T. J.; YOUNG, R. G.; DENNIS, J. E.; CAPLAN, A. I. Optimizing mesenchymal stem cell-based therapeutics. Curr Opin Biotechnol., v. 20, p. 531–536, 2009 DOI: https://doi.org/10.1016/j.copbio.2009.08.009 DOI: https://doi.org/10.1016/j.copbio.2009.08.009
WANG, W.; YUAN, C.; LIU, Z.; GENG, T.; LI, X.; WEI, L.; NIU, W.; WANG, P. Characteristic comparison between canine and human dental mesenchymal stem cells for periodontal regeneration research in preclinical animal studies. Tissue Cell., v. 67, p. 101405, 2020 DOI: https://doi.org/10.1016/j.tice.2020.101405 DOI: https://doi.org/10.1016/j.tice.2020.101405
YAMANAKA, S. Pluripotent stem cell-based cell therapy: Promise and challenges. Cell Stem Cell, v. 27, p. 523–531, 2020 DOI: https://doi.org/10.1016/j.stem.2020.09.011 DOI: https://doi.org/10.1016/j.stem.2020.09.014
ZUK, P. A.; ZHU, M.; ASHJIAN, P.; DE UGARTE, D. A.; HUANG, J. I.; MIZUNO, H.; ALFONSO, Z. C.; FRASER, J. K.; BENHAIM, P.; HEDRICK, M. H. Multilineage cells from human adipose tissue: Implications for cell-based therapies. Tissue Eng., v. 7, p. 211–228, 2001 DOI: https://doi.org/10.1089/107632701300062859 DOI: https://doi.org/10.1089/107632701300062859
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