1887

Abstract

Periodontitis is initiated by hyper-inflammatory responses in the periodontal tissues that generate dysbiotic ecological changes within the microbial communities. As a result, supportive tissues of the tooth are damaged and periodontal attachment is lost. Gingival recession, formation of periodontal pockets with the presence of bleeding, and often suppuration and/or tooth mobility are evident upon clinical examination. These changes may ultimately lead to tooth loss. Mesenchymal stem cells (MSCs) are implicated in controlling periodontal disease progression and have been shown to play a key role in periodontal tissue homeostasis and regeneration. Evidence shows that MSCs interact with subgingival microorganisms and their by-products and modulate the activity of immune cells by either paracrine mechanisms or direct cell-to-cell contact. The aim of this review is to reveal the interactions that take place between microbes and in particular periodontal pathogens and MSCs in order to understand the factors and mechanisms that modulate the regenerative capacity of periodontal tissues and the ability of the host to defend against putative pathogens. The clinical implications of these interactions in terms of anti-inflammatory and paracrine responses of MSCs, anti-microbial properties and alterations in function including their regenerative potential are critically discussed based on literature findings. In addition, future directions to design periodontal research models and study the microbial–stem cell interactions are introduced.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001503
2022-04-22
2024-04-19
Loading full text...

Full text loading...

References

  1. Tonetti MS, Greenwell H, Kornman KS. Staging and grading of periodontitis: Framework and proposal of a new classification and case definition. J Clin Periodontol 2018; 45 Suppl 20:S149–S161 [View Article] [PubMed]
    [Google Scholar]
  2. Loos BG, Van Dyke TE. The role of inflammation and genetics in periodontal disease. Periodontol 2000 2020; 83:26–39 [View Article] [PubMed]
    [Google Scholar]
  3. Friedenstein AJ, Chailakhjan RK, Lalykina KS. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet 1970; 3:393–403 [View Article] [PubMed]
    [Google Scholar]
  4. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8:315–317 [View Article] [PubMed]
    [Google Scholar]
  5. Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 2001; 7:211–228 [View Article] [PubMed]
    [Google Scholar]
  6. Erices A, Conget P, Minguell JJ. Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol 2000; 109:235–242 [View Article] [PubMed]
    [Google Scholar]
  7. Kassis I, Zangi L, Rivkin R, Levdansky L, Samuel S et al. Isolation of mesenchymal stem cells from G-CSF-mobilized human peripheral blood using fibrin microbeads. Bone Marrow Transplant 2006; 37:967–976 [View Article] [PubMed]
    [Google Scholar]
  8. Sharpe PT. Dental mesenchymal stem cells. Development 2016; 143:2273–2280 [View Article] [PubMed]
    [Google Scholar]
  9. Gronthos S, Arthur A, Bartold PM, Shi S. A method to isolate and culture expand human dental pulp stem cells. Methods Mol Biol 2011; 698:107–121 [View Article] [PubMed]
    [Google Scholar]
  10. Akiyama K, Chen C, Gronthos S, Shi S. Lineage differentiation of mesenchymal stem cells from dental pulp, apical papilla, and periodontal ligament. Methods Mol Biol 2012; 887:111–121 [View Article] [PubMed]
    [Google Scholar]
  11. Mason S, Tarle SA, Osibin W, Kinfu Y, Kaigler D. Standardization and safety of alveolar bone-derived stem cell isolation. J Dent Res 2014; 93:55–61 [View Article] [PubMed]
    [Google Scholar]
  12. Wang X, Song H, Zhao S, Guan W, Gao Y. Gingival-derived mesenchymal stem cells protect against sepsis and its complications. Infect Drug Resist 2021; 14:3341–3355 [View Article] [PubMed]
    [Google Scholar]
  13. Castro-Malaspina H, Gay RE, Resnick G, Kapoor N, Meyers P et al. Characterization of human bone marrow fibroblast colony-forming cells (CFU-F) and their progeny. Blood 1980; 56:289–301 [View Article] [PubMed]
    [Google Scholar]
  14. Han J, Menicanin D, Gronthos S, Bartold PM. Stem cells, tissue engineering and periodontal regeneration. Aust Dent J 2014; 59 Suppl 1:117–130 [View Article] [PubMed]
    [Google Scholar]
  15. Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent RL. Microbial complexes in subgingival plaque. J Clin Periodontol 1998; 25:134–144 [View Article] [PubMed]
    [Google Scholar]
  16. Socransky SS, Haffajee AD. Dental biofilms: difficult therapeutic targets. Periodontol 2000 2002; 28:12–55 [View Article] [PubMed]
    [Google Scholar]
  17. Meyer DH, Lippmann JE, Fives-Taylor PM. Invasion of epithelial cells by Actinobacillus actinomycetemcomitans: a dynamic, multistep process. Infect Immun 1996; 64:2988–2997 [View Article] [PubMed]
    [Google Scholar]
  18. Marsh PD. Microbial ecology of dental plaque and its significance in health and disease. Adv Dent Res 1994; 8:263–271 [View Article] [PubMed]
    [Google Scholar]
  19. Lamont RJ, Hajishengallis G. Polymicrobial synergy and dysbiosis in inflammatory disease. Trends Mol Med 2015; 21:172–183 [View Article] [PubMed]
    [Google Scholar]
  20. Fragkioudakis I, Riggio MP, Apatzidou DA. Understanding the microbial components of periodontal diseases and periodontal treatment-induced microbiological shifts. J Med Microbiol 2021; 70:1 [View Article] [PubMed]
    [Google Scholar]
  21. Apatzidou DA, Kinane DF. Nonsurgical mechanical treatment strategies for periodontal disease. Dent Clin North Am 2010; 54:1–12 [View Article] [PubMed]
    [Google Scholar]
  22. Tay JRH, Ng E, Nair R, Tan ZS, Tan SHX. Economic evaluations in the treatment and evaluation of patients with periodontal disease: A critical review. J Clin Periodontol 2021; 48:679–694 [View Article] [PubMed]
    [Google Scholar]
  23. Kinane DF. Single-visit, full-mouth ultrasonic debridement: a paradigm shift in periodontal therapy?. J Clin Periodontol 2005; 32:732–733 [View Article] [PubMed]
    [Google Scholar]
  24. Apatzidou DA, Zygogianni P, Sakellari D, Konstantinidis A. Oral hygiene reinforcement in the simplified periodontal treatment of 1 hour. J Clin Periodontol 2014; 41:149–156 [View Article] [PubMed]
    [Google Scholar]
  25. Apatzidou DA, Riggio MP, Kinane DF. Impact of smoking on the clinical, microbiological and immunological parameters of adult patients with periodontitis. J Clin Periodontol 2005; 32:973–983 [View Article] [PubMed]
    [Google Scholar]
  26. Dommisch H, Kuzmanova D, Jönsson D, Grant M, Chapple I. Effect of micronutrient malnutrition on periodontal disease and periodontal therapy. Periodontol 2000 2018; 78:129–153 [View Article] [PubMed]
    [Google Scholar]
  27. Carra MC, Detzen L, Kitzmann J, Woelber JP, Ramseier CA et al. Promoting behavioural changes to improve oral hygiene in patients with periodontal diseases: A systematic review. J Clin Periodontol 2020; 47 Suppl 22:72–89 [View Article] [PubMed]
    [Google Scholar]
  28. Apatzidou DA. Modern approaches to non-surgical biofilm management. Front Oral Biol 2012; 15:99–116 [View Article] [PubMed]
    [Google Scholar]
  29. Sanz M, Dahlin C, Apatzidou D, Artzi Z, Bozic D et al. Biomaterials and regenerative technologies used in bone regeneration in the craniomaxillofacial region: Consensus report of group 2 of the 15th European Workshop on Periodontology on Bone Regeneration. J Clin Periodontol 2019; 46 Suppl 21:82–91 [View Article] [PubMed]
    [Google Scholar]
  30. Cortellini P. Minimally invasive surgical techniques in periodontal regeneration. J Evid Based Dent Pract 2012; 12:89–100 [View Article] [PubMed]
    [Google Scholar]
  31. Sanz-Sánchez I, Montero E, Citterio F, Romano F, Molina A et al. Efficacy of access flap procedures compared to subgingival debridement in the treatment of periodontitis. A systematic review and meta-analysis. J Clin Periodontol 2020; 47 Suppl 22:282–302 [View Article]
    [Google Scholar]
  32. Stavropoulos A, Bertl K, Spineli LM, Sculean A, Cortellini P et al. Medium- and long-term clinical benefits of periodontal regenerative/reconstructive procedures in intrabony defects: Systematic review and network meta-analysis of randomized controlled clinical studies. J Clin Periodontol 2021; 48:410–430 [View Article]
    [Google Scholar]
  33. Hynes K, Menicanin D, Gronthos S, Bartold PM. Clinical utility of stem cells for periodontal regeneration. Periodontol 2000 2012; 59:203–227 [View Article]
    [Google Scholar]
  34. Xu X-Y, Li X, Wang J, He X-T, Sun H-H et al. Concise review: periodontal tissue regeneration using stem cells: strategies and translational considerations. Stem Cells Transl Med 2019; 8:392–403 [View Article]
    [Google Scholar]
  35. Bartold PM. Lifestyle and periodontitis: The emergence of personalized periodontics. Periodontol 2000 2018; 78:7–11 [View Article]
    [Google Scholar]
  36. Polimeni G, Xiropaidis AV, Wikesjö UME. Biology and principles of periodontal wound healing/regeneration. Periodontol 2000 2006; 41:30–47 [View Article]
    [Google Scholar]
  37. Krafts KP. Tissue repair: The hidden drama. Organogenesis 2010; 6:225–233 [View Article]
    [Google Scholar]
  38. Prichard J. Regeneration of bone following periodontal therapy. report of cases. Oral Surg Oral Med Oral Pathol 1957; 10:247–252 [View Article]
    [Google Scholar]
  39. Sculean A, Nikolidakis D, Nikou G, Ivanovic A, Chapple ILC et al. Biomaterials for promoting periodontal regeneration in human intrabony defects: a systematic review. Periodontol 2000 2015; 68:182–216 [View Article]
    [Google Scholar]
  40. Aukhil I. Biology of wound healing. Periodontol 2000 2000; 22:44–50 [View Article]
    [Google Scholar]
  41. Ding DC, Shyu WC, Lin SZ. Mesenchymal stem cells. Cell Transplant 2011; 20:5–14 [View Article] [PubMed]
    [Google Scholar]
  42. Vizoso FJ, Eiro N, Costa L, Esparza P, Landin M et al. Mesenchymal stem cells in homeostasis and systemic diseases: hypothesis, evidences, and therapeutic opportunities. Int J Mol Sci 2019; 20:3738 [View Article] [PubMed]
    [Google Scholar]
  43. Ouchi T, Nakagawa T. Mesenchymal stem cell-based tissue regeneration therapies for periodontitis. Regen Ther 2020; 14:72–78 [View Article] [PubMed]
    [Google Scholar]
  44. Gao F, Chiu SM, Motan DAL, Zhang Z, Chen L et al. Mesenchymal stem cells and immunomodulation: current status and future prospects. Cell Death Dis 2016; 7:e2062 [View Article] [PubMed]
    [Google Scholar]
  45. Meijer GJ, de Bruijn JD, Koole R, van Blitterswijk CA. Cell based bone tissue engineering in jaw defects. Biomaterials 2008; 29:3053–3061 [View Article] [PubMed]
    [Google Scholar]
  46. Gjerde C, Mustafa K, Hellem S, Rojewski M, Gjengedal H et al. Cell therapy induced regeneration of severely atrophied mandibular bone in a clinical trial. Stem Cell Res Ther 2018; 9:213 [View Article] [PubMed]
    [Google Scholar]
  47. Shanbhag S, Suliman S, Pandis N, Stavropoulos A, Sanz M et al. Cell therapy for orofacial bone regeneration: A systematic review and meta-analysis. J Clin Periodontol 2019; 46 Suppl 21:162–182 [View Article] [PubMed]
    [Google Scholar]
  48. Apatzidou DA, Bakopoulou AA, Kouzi-Koliakou K, Karagiannis V, Konstantinidis A. A tissue-engineered biocomplex for periodontal reconstruction. A proof-of-principle randomized clinical study. J Clin Periodontol 2021; 48:1111–1125 [View Article] [PubMed]
    [Google Scholar]
  49. Nuñez J, Vignoletti F, Caffesse RG, Sanz M. Cellular therapy in periodontal regeneration. Periodontol 2000 2019; 79:107–116 [View Article]
    [Google Scholar]
  50. Rojewski MT, Lotfi R, Gjerde C, Mustafa K, Veronesi E et al. Translation of a standardized manufacturing protocol for mesenchymal stromal cells: A systematic comparison of validation and manufacturing data. Cytotherapy 2019; 21:468–482 [View Article] [PubMed]
    [Google Scholar]
  51. de Almeida Fuzeta M, de Matos Branco AD, Fernandes-Platzgummer A, da Silva CL, Cabral JMS. Addressing the manufacturing challenges of cell-based therapies. Adv Biochem Eng Biotechnol 2020; 171:225–278 [View Article] [PubMed]
    [Google Scholar]
  52. Chaparro Padilla A, Weber Aracena L, Realini Fuentes O, Albers Busquetts D, Hernández Ríos M et al. Molecular signatures of extracellular vesicles in oral fluids of periodontitis patients. Oral Dis 2020; 26:1318–1325 [View Article] [PubMed]
    [Google Scholar]
  53. Jia L, Han N, Du J, Guo L, Luo Z et al. Pathogenesis of Important Virulence Factors of Porphyromonas gingivalis via Toll-Like Receptors. Front Cell Infect Microbiol 2019; 9:262 [View Article] [PubMed]
    [Google Scholar]
  54. Ginsburg I. Role of lipoteichoic acid in infection and inflammation. Lancet Infect Dis 2002; 2:171–179 [View Article] [PubMed]
    [Google Scholar]
  55. Franco C, Patricia H-R, Timo S, Claudia B, Marcela H. Matrix metalloproteinases as regulators of periodontal inflammation. Int J Mol Sci 2017; 18:440 [View Article] [PubMed]
    [Google Scholar]
  56. Keles Yucel ZP, Afacan B, Emingil G, Tervahartiala T, Kose T et al. Local and systemic levels of aMMP-8 in gingivitis and stage 3 grade C periodontitis. J Periodontal Res 2020; 55:887–894 [View Article] [PubMed]
    [Google Scholar]
  57. Bostanci N, Belibasakis GN. Porphyromonas gingivalis: an invasive and evasive opportunistic oral pathogen. FEMS Microbiol Lett 2012; 333:1–9 [View Article] [PubMed]
    [Google Scholar]
  58. Tsai C-C, Ho Y-P, Chou Y-S, Ho K-Y, Wu Y-M et al. Aggregatibacter (Actinobacillus) actimycetemcomitans leukotoxin and human periodontitis - A historic review with emphasis on JP2. Kaohsiung J Med Sci 2018; 34:186–193 [View Article] [PubMed]
    [Google Scholar]
  59. Greabu M, Totan A, Miricescu D, Radulescu R, Virlan J et al. Hydrogen Sulfide, Oxidative Stress and Periodontal Diseases: A Concise Review. Antioxidants (Basel) 2016; 5:3 [View Article] [PubMed]
    [Google Scholar]
  60. Darveau RP, Pham T-TT, Lemley K, Reife RA, Bainbridge BW et al. Porphyromonas gingivalis lipopolysaccharide contains multiple lipid A species that functionally interact with both toll-like receptors 2 and 4. Infect Immun 2004; 72:5041–5051 [View Article] [PubMed]
    [Google Scholar]
  61. Wang PL, Ohura K. Porphyromonas gingivalis lipopolysaccharide signaling in gingival fibroblasts-CD14 and Toll-like receptors. Crit Rev Oral Biol Med 2002; 13:132–142 [View Article]
    [Google Scholar]
  62. Groeger S, Meyle J. Oral Mucosal Epithelial Cells. Front Immunol 2019; 10:208 [View Article]
    [Google Scholar]
  63. Andrukhov O, Andrukhova O, Özdemir B, Haririan H, Müller-Kern M et al. Soluble CD14 Enhances the Response of Periodontal Ligament Stem Cells to P. gingivalis Lipopolysaccharide. PLoS One 2016; 11:e0160848 [View Article]
    [Google Scholar]
  64. Beutler B, Rietschel ET. Innate immune sensing and its roots: the story of endotoxin. Nat Rev Immunol 2003; 3:169–176 [View Article]
    [Google Scholar]
  65. Zanoni I, Ostuni R, Marek LR, Barresi S, Barbalat R et al. CD14 controls the LPS-induced endocytosis of Toll-like receptor 4. Cell 2011; 147:868–880 [View Article]
    [Google Scholar]
  66. Behm C, Blufstein A, Gahn J, Noroozkhan N, Moritz A et al. Soluble CD14 Enhances the Response of Periodontal Ligament Stem Cells to Toll-Like Receptor 2 Agonists. Mediators Inflamm 2019; 2019:8127301 [View Article] [PubMed]
    [Google Scholar]
  67. Blufstein A, Behm C, Gahn J, Uitz O, Naumovska I et al. Synergistic effects triggered by simultaneous Toll-like receptor-2 and -3 activation in human periodontal ligament stem cells. J Periodontol 2019; 90:1190–1201 [View Article] [PubMed]
    [Google Scholar]
  68. Diomede F, Zingariello M, Cavalcanti MFXB, Merciaro I, Pizzicannella J et al. MyD88/ERK/NFkB pathways and pro-inflammatory cytokines release in periodontal ligament stem cells stimulated by Porphyromonas gingivalis. Eur J Histochem 2017; 61:2791 [View Article] [PubMed]
    [Google Scholar]
  69. Gölz L, Memmert S, Rath-Deschner B, Jäger A, Appel T et al. Hypoxia and P. gingivalis synergistically induce HIF-1 and NF-;B activation in PDL cells and periodontal diseases. Mediators Inflamm 2015; 2015:438085 [View Article] [PubMed]
    [Google Scholar]
  70. Jian C, Li C, Ren Y, He Y, Li Y et al. Hypoxia augments lipopolysaccharide-induced cytokine expression in periodontal ligament cells. Inflammation 2014; 37:1413–1423 [View Article] [PubMed]
    [Google Scholar]
  71. Ramenzoni LL, Russo G, Moccia MD, Attin T, Schmidlin PR. Periodontal bacterial supernatants modify differentiation, migration and inflammatory cytokine expression in human periodontal ligament stem cells. PLoS One 2019; 14:e0219181 [View Article] [PubMed]
    [Google Scholar]
  72. Sriram G, Natu VP, Islam I, Fu X, Seneviratne CJ et al. Innate Immune Response of Human Embryonic Stem Cell-Derived Fibroblasts and Mesenchymal Stem Cells to Periodontopathogens. Stem Cells Int 2016; 2016:8905365 [View Article] [PubMed]
    [Google Scholar]
  73. Albiero ML, Amorim BR, Casati MZ, Sallum EA, Nociti FH Junior et al. Osteogenic potential of periodontal ligament stem cells are unaffected after exposure to lipopolysaccharides. Braz Oral Res 2017; 31:e17 [View Article] [PubMed]
    [Google Scholar]
  74. Albiero ML, Stipp RN, Saito MT, Casati MZ, Sallum EA et al. Viability and Osteogenic Differentiation of Human Periodontal Ligament Progenitor Cells Are Maintained After Incubation With Porphyromonas gingivalis Protein Extract. J Periodontol 2017; 88:e188–e199 [View Article] [PubMed]
    [Google Scholar]
  75. Guan S-M, Zhang M, He J-J, Wu J-Z. Mitogen-activated protein kinases and phosphatidylinositol 3-kinase are involved in Prevotella intermedia-induced proinflammatory cytokines expression in human periodontal ligament cells. Biochem Biophys Res Commun 2009; 386:471–476 [View Article] [PubMed]
    [Google Scholar]
  76. Zhang W, Liu HT. MAPK signal pathways in the regulation of cell proliferation in mammalian cells. Cell Res 2002; 12:9–18 [View Article] [PubMed]
    [Google Scholar]
  77. Reddi D, Belibasakis GN. Transcriptional profiling of bone marrow stromal cells in response to Porphyromonas gingivalis secreted products. PLoS One 2012; 7:e43899 [View Article] [PubMed]
    [Google Scholar]
  78. Su W, Shi J, Zhao Y, Yan F, Lei L et al. Porphyromonas gingivalis triggers inflammatory responses in periodontal ligament cells by succinate-succinate dehydrogenase-HIF-1α axis. Biochem Biophys Res Commun 2020; 522:184–190 [View Article] [PubMed]
    [Google Scholar]
  79. Morsczeck CO, Drees J, Dress J, Gosau M. Lipopolysaccharide from Escherichia coli but not from Porphyromonas gingivalis induce pro-inflammatory cytokines and alkaline phosphatase in dental follicle cells. Arch Oral Biol 2012; 57:1595–1601 [View Article] [PubMed]
    [Google Scholar]
  80. Biedermann A, Kriebel K, Kreikemeyer B, Lang H. Interactions of anaerobic bacteria with dental stem cells: an in vitro study. PLoS One 2014; 9:e110616 [View Article] [PubMed]
    [Google Scholar]
  81. Chatzivasileiou K, Lux CA, Steinhoff G, Lang H. Dental follicle progenitor cells responses to Porphyromonas gingivalis LPS. J Cell Mol Med 2013; 17:766–773 [View Article] [PubMed]
    [Google Scholar]
  82. Nociti FH, Foster BL, Barros SP, Darveau RP, Somerman MJ. Cementoblast gene expression is regulated by Porphyromonas gingivalis lipopolysaccharide partially via toll-like receptor-4/MD-2. J Dent Res 2004; 83:602–607 [View Article] [PubMed]
    [Google Scholar]
  83. Morsczeck C, Götz W, Schierholz J, Zeilhofer F, Kühn U et al. Isolation of precursor cells (PCs) from human dental follicle of wisdom teeth. Matrix Biol 2005; 24:155–165 [View Article] [PubMed]
    [Google Scholar]
  84. Nagatomo K, Komaki M, Sekiya I, Sakaguchi Y, Noguchi K et al. Stem cell properties of human periodontal ligament cells. J Periodontal Res 2006; 41:303–310 [View Article] [PubMed]
    [Google Scholar]
  85. Francis M, Pandya M, Gopinathan G, Lyu H, Ma W et al. Histone Methylation Mechanisms Modulate the Inflammatory Response of Periodontal Ligament Progenitors. Stem Cells Dev 2019; 28:1015–1025 [View Article] [PubMed]
    [Google Scholar]
  86. Xing Y, Zhang Y, Jia L, Xu X. Lipopolysaccharide from Escherichia coli stimulates osteogenic differentiation of human periodontal ligament stem cells through Wnt/β‐catenin–induced TAZ elevation. Mol Oral Microbiol 2018; 34:1 [View Article]
    [Google Scholar]
  87. Hieke C, Kriebel K, Engelmann R, Müller-Hilke B, Lang H et al. Human dental stem cells suppress PMN activity after infection with the periodontopathogens Prevotella intermedia and Tannerella forsythia. Sci Rep 2016; 6:39096 [View Article] [PubMed]
    [Google Scholar]
  88. Kang W, Ji X, Zhang X, Tang D, Feng Q. Persistent Exposure to Fusobacterium nucleatum Triggers Chemokine/Cytokine Release and Inhibits the Proliferation and Osteogenic Differentiation Capabilities of Human Gingiva-Derived Mesenchymal Stem Cells. Front Cell Infect Microbiol 2019; 9:429 [View Article] [PubMed]
    [Google Scholar]
  89. Keong JY, Low LW, Chong JM, Ong YY, Pulikkotil SJ et al. Effect of lipopolysaccharide on cell proliferation and vascular endothelial growth factor secretion of periodontal ligament stem cells. Saudi Dent J 2020; 32:148–154 [View Article] [PubMed]
    [Google Scholar]
  90. Albiero ML, Amorim BR, Martins L, Casati MZ, Sallum EA et al. Exposure of periodontal ligament progenitor cells to lipopolysaccharide from Escherichia coli changes osteoblast differentiation pattern. J Appl Oral Sci 2015; 23:145–152 [View Article] [PubMed]
    [Google Scholar]
  91. Lee JH, Um S, Jang JH, Seo BM. Effects of VEGF and FGF-2 on proliferation and differentiation of human periodontal ligament stem cells. Cell Tissue Res 2012; 348:475–484 [View Article] [PubMed]
    [Google Scholar]
  92. Mo IFY, Yip KHK, Chan WK, Law HKW, Lau YL et al. Prolonged exposure to bacterial toxins downregulated expression of toll-like receptors in mesenchymal stromal cell-derived osteoprogenitors. BMC Cell Biol 2008; 9:52 [View Article] [PubMed]
    [Google Scholar]
  93. Tang J, Wu T, Xiong J, Su Y, Zhang C et al. Porphyromonas gingivalis lipopolysaccharides regulate functions of bone marrow mesenchymal stem cells. Cell Prolif 2015; 48:239–248 [View Article] [PubMed]
    [Google Scholar]
  94. Kadono H, Kido JI, Kataoka M, Yamauchi N, Nagata T. Inhibition of osteoblastic cell differentiation by lipopolysaccharide extract from Porphyromonas gingivalis. Infect Immun 1999; 67:2841–2846 [View Article] [PubMed]
    [Google Scholar]
  95. Kato H, Taguchi Y, Tominaga K, Umeda M, Tanaka A. Porphyromonas gingivalis LPS inhibits osteoblastic differentiation and promotes pro-inflammatory cytokine production in human periodontal ligament stem cells. Arch Oral Biol 2014; 59:167–175 [View Article] [PubMed]
    [Google Scholar]
  96. Xing Q, Ye Q, Fan M, Zhou Y, Xu Q et al. Porphyromonas gingivalis lipopolysaccharide inhibits the osteoblastic differentiation of preosteoblasts by activating Notch1 signaling. J Cell Physiol 2010; 225:106–114 [View Article] [PubMed]
    [Google Scholar]
  97. Han N, Jia L, Guo L, Su Y, Luo Z et al. Balanced oral pathogenic bacteria and probiotics promoted wound healing via maintaining mesenchymal stem cell homeostasis. Stem Cell Res Ther 2020; 11:61 [View Article] [PubMed]
    [Google Scholar]
  98. Kukolj T, Trivanović D, Djordjević IO, Mojsilović S, Krstić J et al. Lipopolysaccharide can modify differentiation and immunomodulatory potential of periodontal ligament stem cells via ERK1,2 signaling. J Cell Physiol 2018; 233:447–462 [View Article] [PubMed]
    [Google Scholar]
  99. Zheng W, Wang S, Wang J, Jin F. Periodontitis promotes the proliferation and suppresses the differentiation potential of human periodontal ligament stem cells. Int J Mol Med 2015; 36:915–922 [View Article] [PubMed]
    [Google Scholar]
  100. Calenic B, Yaegaki K, Ishkitiev N, Kumazawa Y, Imai T et al. p53-Pathway activity and apoptosis in hydrogen sulfide-exposed stem cells separated from human gingival epithelium. J Periodontal Res 2013; 48:322–330 [View Article] [PubMed]
    [Google Scholar]
  101. Morita M, Wang HL. Association between oral malodor and adult periodontitis: a review. J Clin Periodontol 2001; 28:813–819 [View Article]
    [Google Scholar]
  102. Vousden KH, Prives C. Blinded by the light: the growing complexity of p53. Cell 2009; 137:413–431 [View Article]
    [Google Scholar]
  103. Calenic B, Yaegaki K, Kozhuharova A, Imai T. Oral malodorous compound causes oxidative stress and p53-mediated programmed cell death in keratinocyte stem cells. J Periodontol 2010; 81:1317–1323 [View Article]
    [Google Scholar]
  104. Ha NH, Woo BH, Kim DJ, Ha ES, Choi JI et al. Prolonged and repetitive exposure to Porphyromonas gingivalis increases aggressiveness of oral cancer cells by promoting acquisition of cancer stem cell properties. Tumour Biol 2015; 36:9947–9960 [View Article]
    [Google Scholar]
  105. Bostanci N, Belibasakis GN. Porphyromonas gingivalis: an invasive and evasive opportunistic oral pathogen. FEMS Microbiol Lett 2012; 333:1–9 [View Article]
    [Google Scholar]
  106. Pan C, Liu J, Wang H, Song J, Tan L et al. Porphyromonas gingivalis can invade periodontal ligament stem cells. BMC Microbiol 2017; 17:38 [View Article] [PubMed]
    [Google Scholar]
  107. Amornchat C, Rassameemasmaung S, Sripairojthikoon W, Swasdison S. Invasion of Porphyromonas gingivalis into human gingival fibroblasts in vitro. J Int Acad Periodontol 2003; 5:98–105 [PubMed]
    [Google Scholar]
  108. Irshad M, van der Reijden WA, Crielaard W, Laine ML. In vitro invasion and survival of Porphyromonas gingivalis in gingival fibroblasts; role of the capsule. Arch Immunol Ther Exp (Warsz) 2012; 60:469–476 [View Article] [PubMed]
    [Google Scholar]
  109. Pan C, Liu J, Wang H, Song J, Tan L et al. Porphyromonas gingivalis can invade periodontal ligament stem cells. BMC Microbiol 2017; 17:38 [View Article] [PubMed]
    [Google Scholar]
  110. Brennan MÁ., Layrolle P, Mooney DJ. Biomaterials functionalized with MSC secreted extracellular vesicles and soluble factors for tissue regeneration. Adv Funct Mater 2020; 30:37 [View Article] [PubMed]
    [Google Scholar]
  111. Volarevic V, Gazdic M, Simovic Markovic B, Jovicic N, Djonov V et al. Mesenchymal stem cell-derived factors: Immuno-modulatory effects and therapeutic potential. Biofactors 2017; 43:633–644 [View Article] [PubMed]
    [Google Scholar]
  112. Caplan AI. Mesenchymal stem cells: time to change the name!. Stem Cells Transl Med 2017; 6:1445–1451 [View Article] [PubMed]
    [Google Scholar]
  113. Humbert P, Brennan , Davison N, Rosset P, Trichet V et al. Immune modulation by transplanted calcium phosphate biomaterials and human mesenchymal stromal cells in bone regeneration. Front Immunol 2019; 10:663 [View Article] [PubMed]
    [Google Scholar]
  114. Haumer A, Bourgine PE, Occhetta P, Born G, Tasso R et al. Delivery of cellular factors to regulate bone healing. Adv Drug Deliv Rev 2018; 129:285–294 [View Article] [PubMed]
    [Google Scholar]
  115. Budoni M, Fierabracci A, Luciano R, Petrini S, Di Ciommo V et al. The immunosuppressive effect of mesenchymal stromal cells on B lymphocytes is mediated by membrane vesicles. Cell Transplant 2013; 22:369–379 [View Article] [PubMed]
    [Google Scholar]
  116. Del Fattore A, Luciano R, Pascucci L, Goffredo BM, Giorda E et al. Immunoregulatory effects of mesenchymal stem cell-derived extracellular vesicles on T Lymphocytes. Cell Transplant 2015; 24:2615–2627 [View Article]
    [Google Scholar]
  117. Cheng Y, Cao X, Qin L. Mesenchymal stem cell-derived extracellular vesicles: a novel cell-free therapy for sepsis. Front Immunol 2020; 11:647 [View Article]
    [Google Scholar]
  118. Zheng G, Huang R, Qiu G, Ge M, Wang J et al. Mesenchymal stromal cell-derived extracellular vesicles: regenerative and immunomodulatory effects and potential applications in sepsis. Cell Tissue Res 2018; 374:1–15 [View Article]
    [Google Scholar]
  119. Luan X, Zhou X, Trombetta-eSilva J, Francis M, Gaharwar AK et al. MicroRNAs and Periodontal Homeostasis. J Dent Res 2017; 96:491–500 [View Article]
    [Google Scholar]
  120. Zhou X, Luan X, Chen Z, Francis M, Gopinathan G et al. MicroRNA-138 Inhibits Periodontal Progenitor Differentiation under Inflammatory Conditions. J Dent Res 2016; 95:230–237 [View Article]
    [Google Scholar]
  121. Luan X, Dangaria S, Ito Y, Walker CG, Jin T et al. Critical reviews in oral biology & medicine: neural crest lineage segregation: a blueprint for periodontal regeneration. J Dent Res 2009; 88:781–791 [View Article]
    [Google Scholar]
  122. Zhu M, Miao B, Zhu J, Wang H, Zhou Z. Expression and antimicrobial character of cells transfected with human β‑defensin‑3 against periodontitis‑associated microbiota in vitro. Mol Med Rep 2017; 16:2455–2460 [View Article]
    [Google Scholar]
  123. Krasnodembskaya A, Song Y, Fang X, Gupta N, Serikov V et al. Antibacterial effect of human mesenchymal stem cells is mediated in part from secretion of the antimicrobial peptide LL-37. Stem Cells 2010; 28:2229–2238 [View Article]
    [Google Scholar]
  124. Meisel R, Zibert A, Laryea M, Göbel U, Däubener W et al. Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. Blood 2004; 103:4619–4621 [View Article]
    [Google Scholar]
  125. Su Y, Chen C, Guo L, Du J, Li X et al. Ecological Balance of Oral Microbiota Is Required to Maintain Oral Mesenchymal Stem Cell Homeostasis. Stem Cells 2018; 36:551–561 [View Article]
    [Google Scholar]
  126. Peng W, Deng W, Zhang J, Pei G, Rong Q et al. Long noncoding RNA ANCR suppresses bone formation of periodontal ligament stem cells via sponging miRNA-758. Biochem Biophys Res Commun 2018; 503:815–821 [View Article] [PubMed]
    [Google Scholar]
  127. Apatzidou DA, Nile C, Bakopoulou A, Konstantinidis A, Lappin DF. Stem cell-like populations and immunoregulatory molecules in periodontal granulation tissue. J Periodontal Res 2018; 53:610–621 [View Article] [PubMed]
    [Google Scholar]
  128. Ronay V, Belibasakis GN, Schmidlin PR, Bostanci N. Infected periodontal granulation tissue contains cells expressing embryonic stem cell markers. A pilot study. Schweiz Monatsschr Zahnmed 2013; 123:12–16 [PubMed]
    [Google Scholar]
  129. Yamagishi VT-K, Torneck CD, Friedman S, Huang GTJ, Glogauer M. Blockade of TLR2 inhibits Porphyromonas gingivalis suppression of mineralized matrix formation by human dental pulp stem cells. J Endod 2011; 37:812–818 [View Article] [PubMed]
    [Google Scholar]
  130. Nomiyama K, Kitamura C, Tsujisawa T, Nagayoshi M, Morotomi T et al. Effects of lipopolysaccharide on newly established rat dental pulp-derived cell line with odontoblastic properties. J Endod 2007; 33:1187–1191 [View Article] [PubMed]
    [Google Scholar]
  131. Sanchez CJ, Ward CL, Romano DR, Hurtgen BJ, Hardy SK et al. Staphylococcus aureus biofilms decrease osteoblast viability, inhibits osteogenic differentiation, and increases bone resorption in vitro. BMC Musculoskelet Disord 2013; 14:187 [View Article] [PubMed]
    [Google Scholar]
  132. Kol A, Foutouhi S, Walker NJ, Kong NT, Weimer BC et al. Gastrointestinal microbes interact with canine adipose-derived mesenchymal stem cells in vitro and enhance immunomodulatory functions. Stem Cells Dev 2014; 23:1831–1843 [View Article] [PubMed]
    [Google Scholar]
  133. O’Rourke F, Kempf VAJ. Interaction of bacteria and stem cells in health and disease. FEMS Microbiol Rev 2019; 43:162–180 [View Article] [PubMed]
    [Google Scholar]
  134. Stavropoulos A, Windisch P, Gera I, Capsius B, Sculean A et al. A phase IIa randomized controlled clinical and histological pilot study evaluating rhGDF-5/β-TCP for periodontal regeneration. J Clin Periodontol 2011; 38:1044–1054 [View Article] [PubMed]
    [Google Scholar]
  135. Abusleme L, Hoare A, Hong BY, Diaz PI. Microbial signatures of health, gingivitis, and periodontitis. Periodontol 2000 2021; 86:57–78 [View Article] [PubMed]
    [Google Scholar]
  136. Struillou X, Boutigny H, Soueidan A, Layrolle P. Experimental animal models in periodontology: a review. Open Dent J 2010; 4:37–47 [View Article] [PubMed]
    [Google Scholar]
  137. Langer R, Vacanti JP. Tissue engineering. Science 1993; 260:920–926 [View Article] [PubMed]
    [Google Scholar]
  138. Sriram G, Bigliardi PL, Bigliardi-Qi M. Full-thickness human skin equivalent models of atopic dermatitis. Methods Mol Biol 2019; 1879:367–383 [View Article] [PubMed]
    [Google Scholar]
  139. Semlin L, Schäfer-Korting M, Borelli C, Korting HC. In vitro models for human skin disease. Drug Discov Today 2011; 16:132–139 [View Article] [PubMed]
    [Google Scholar]
  140. Shang L, Deng D, Buskermolen JK, Roffel S, Janus MM et al. Commensal and pathogenic biofilms alter toll-like receptor signaling in reconstructed human gingiva. Front Cell Infect Microbiol 2019; 9:282 [View Article] [PubMed]
    [Google Scholar]
  141. Gibbs S, Roffel S, Meyer M, Gasser A. Biology of soft tissue repair: gingival epithelium in wound healing and attachment to the tooth and abutment surface. Eur Cell Mater 2019; 38:63–78 [View Article] [PubMed]
    [Google Scholar]
  142. Tabatabaei F, Moharamzadeh K, Tayebi L. Three-Dimensional In Vitro Oral Mucosa Models of Fungal and Bacterial Infections. Tissue Eng Part B Rev 2020; 26:443–460 [View Article] [PubMed]
    [Google Scholar]
  143. Barker E, AlQobaly L, Shaikh Z, Franklin K, Moharamzadeh K. Implant Soft-Tissue Attachment Using 3D Oral Mucosal Models-A Pilot Study. Dent J (Basel) 2020; 8:72 [View Article] [PubMed]
    [Google Scholar]
  144. Nishiyama K, Akagi T, Iwai S, Akashi M. Construction of vascularized oral mucosa equivalents using a layer-by-layer cell coating technology. Tissue Eng Part C Methods 2019; 25:262–275 [View Article] [PubMed]
    [Google Scholar]
  145. Nesic D, Schaefer BM, Sun Y, Saulacic N, Sailer I. 3D Printing Approach in Dentistry: The Future for Personalized Oral Soft Tissue Regeneration. J Clin Med 2020; 9:2238 [View Article] [PubMed]
    [Google Scholar]
  146. Ingendoh-Tsakmakidis A, Mikolai C, Winkel A, Szafrański SP, Falk CS et al. Commensal and pathogenic biofilms differently modulate peri-implant oral mucosa in an organotypic model. Cell Microbiol 2019; 21:e13078 [View Article] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.001503
Loading
/content/journal/jmm/10.1099/jmm.0.001503
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error