Stem Cells in the Periodontium—Anatomically Related Yet Physiologically Diverse

 

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Abstract

Periodontitis is a complex chronic disease discernible by the deterioration of periodontal tissue. The goal of periodontal therapy is to achieve complete tissue regeneration, and one of the most promising treatment options is to harness the regenerative potential of stem cells available within the periodontal complex. Periodontal ligament stem cells, gingival mesenchymal stem cells, oral periosteal stem cells, and dental follicle stem cells have structural similarities, but their immunological responses and features differ. The qualities of diverse periodontal stem cells, their immune-modulatory effects, and variances in their phenotypes and characteristics will be discussed in this review. Although there is evidence on each stem cell population in the periodontium, understanding the differences in markers expressed, the various research conducted so far on their regenerative potential, will help in understanding which stem cell population will be a better candidate for tissue engineering. The possibility of selecting the most amenable stem cell population for optimal periodontal regeneration and the development and current application of superior tissue engineering treatment options such as autologous transplantation, three-dimensional bioengineered scaffolds, dental stem cell-derived extracellular vesicles will be explored.

Publication History

Article published online:
31 December 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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• References

• 1 Cekici A, Kantarci A, Hasturk H, Van Dyke TE. Inflammatory and immune pathways in the pathogenesis of periodontal disease. Periodontol 2000 2014; 64 (01) 57-80
  CrossrefPubMedGoogle Scholar
• 2 Van der Weijden GAF, Dekkers GJ, Slot DE. Success of non-surgical periodontal therapy in adult periodontitis patients: a retrospective analysis. Int J Dent Hyg 2019; 17 (04) 309-317
  CrossrefPubMedGoogle Scholar
• 3 Liang Y, Luan X, Liu X. Recent advances in periodontal regeneration: a biomaterial perspective. Bioact Mater 2020; 5 (02) 297-308
  CrossrefPubMedGoogle Scholar
• 4 Wang M, Xie J, Wang C, Zhong D, Xie L, Fang H. Immunomodulatory properties of stem cells in periodontitis: current status and future prospective. Stem Cells Int 2020; 2020: 9836518 DOI: 10.1155/2020/9836518.
  CrossrefPubMedGoogle Scholar
• 5 Citterio F, Gualini G, Fierravanti L, Aimetti M. Stem cells and periodontal regeneration: present and future. Plast Aesthet Res 2020; 7: 41 DOI: 10.20517/2347-9264.2020.29.
  CrossrefGoogle Scholar
• 6 Isern J, García-García A, Martín AM. et al. The neural crest is a source of mesenchymal stem cells with specialized hematopoietic stem cell niche function. eLife 2014; 3: e03696 DOI: 10.7554/eLife.03696.
  CrossrefPubMedGoogle Scholar
• 7 Wang L, Shen H, Zheng W. et al. Characterization of stem cells from alveolar periodontal ligament. Tissue Eng Part A 2011; 17 (7-8): 1015-1026
  CrossrefPubMedGoogle Scholar
• 8 Seo BM, Miura M, Gronthos S. et al. Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 2004; 364 (9429): 149-155
  CrossrefPubMedGoogle Scholar
• 9 Nugraha AP, Narmada IB, Ernawati DS. et al. Osteogenic potential of gingival stromal progenitor cells cultured in platelet rich fibrin is predicted by core-binding factor subunit-α1/Sox9 expression ratio ( in vitro). F1000 Res 2018; 7: 1134 DOI: 10.12688/f1000research.15423.1.
  CrossrefPubMedGoogle Scholar
• 10 Al-Qadhi G, Al-Rai S, Hafed L. The therapeutic potential of inflamed gingiva-derived mesenchymal stem cells in preclinical studies: a scoping review of a unique biomedical waste. Stem Cells Int 2021; 2021: 6619170 DOI: 10.1155/2021/6619170.
  CrossrefPubMedGoogle Scholar
• 11 Morsczeck C, Götz W, Schierholz J. et al. Isolation of precursor cells (PCs) from human dental follicle of wisdom teeth. Matrix Biol 2005; 24 (02) 155-165
  CrossrefPubMedGoogle Scholar
• 12 Zhang J, Ding H, Liu X, Sheng Y, Liu X, Jiang C. Dental follicle stem cells: tissue engineering and immunomodulation. Stem Cells Dev 2019; 28 (15) 986-994
  CrossrefPubMedGoogle Scholar
• 13 Saimbi CS, Gautam A, Khan MA. , Nandlal. Periosteum as a barrier membrane in the treatment of intrabony defect: a new technique. J Indian Soc Periodontol 2014; 18 (03) 331-335
  CrossrefPubMedGoogle Scholar
• 14 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 DOI: 10.1155/2020/1327405.
  CrossrefPubMedGoogle Scholar
• 15 Fournier BPJ, Larjava H, Häkkinen L. Gingiva as a source of stem cells with therapeutic potential. Stem Cells Dev 2013; 22 (24) 3157-3177
  CrossrefPubMedGoogle Scholar
• 16 Stefańska K, Mehr K, Wieczorkiewicz M. et al. Stemness potency of human gingival cells-application in anticancer therapies and clinical trials. Cells 2020; 9 (08) E1916 DOI: 10.3390/cells9081916.
  CrossrefPubMedGoogle Scholar
• 17 Keating A. Mesenchymal stromal cells: new directions. Cell Stem Cell 2012; 10 (06) 709-716
  CrossrefPubMedGoogle Scholar
• 18 Huang GTJ, 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; 88 (09) 792-806
  CrossrefPubMedGoogle Scholar
• 19 Fawzy El-Sayed KM, Dörfer CE. Gingival mesenchymal stem/progenitor cells: a unique tissue engineering gem. Stem Cells Int 2016; 2016: 7154327 DOI: 10.1155/2016/7154327.
  CrossrefPubMedGoogle Scholar
• 20 Zhang N, Hu L, Cao Z, Liu X, Pan J. Periosteal skeletal stem cells and their response to bone injury. Front Cell Dev Biol 2022; 10: 812094 DOI: 10.3389/fcell.2022.812094.
  CrossrefPubMedGoogle Scholar
• 21 Kaku M, Komatsu Y, Mochida Y, Yamauchi M, Mishina Y, Ko C-C. Identification and characterization of neural crest-derived cells in adult periodontal ligament of mice. Arch Oral Biol 2012; 57 (12) 1668-1675
  CrossrefPubMedGoogle Scholar
• 22 Zhang Q, Nguyen AL, Shi S. et al. Three-dimensional spheroid culture of human gingiva-derived mesenchymal stem cells enhances mitigation of chemotherapy-induced oral mucositis. Stem Cells Dev 2012; 21 (06) 937-947
  CrossrefPubMedGoogle Scholar
• 23 Lima RL, Holanda-Afonso RC, Moura-Neto V, Bolognese AM, DosSantos MF, Souza MM. Human dental follicle cells express embryonic, mesenchymal and neural stem cells markers. Arch Oral Biol 2017; 73: 121-128
  CrossrefPubMedGoogle Scholar
• 24 Ichikawa Y, Watahiki J, Nampo T. et al. Differences in the developmental origins of the periosteum may influence bone healing. J Periodontal Res 2015; 50 (04) 468-478
  CrossrefPubMedGoogle Scholar
• 25 Ceccarelli G, Graziano A, Benedetti L. et al. Osteogenic potential of human oral-periosteal cells (PCs) isolated from different oral origin: an in vitro study. J Cell Physiol 2016; 231 (03) 607-612
  CrossrefPubMedGoogle Scholar
• 26 Suphanantachat S, Iwata T, Ishihara J, Yamato M, Okano T, Izumi Y. A role for c-Kit in the maintenance of undifferentiated human mesenchymal stromal cells. Biomaterials 2014; 35 (11) 3618-3626
  CrossrefPubMedGoogle Scholar
• 27 Debnath S, Yallowitz AR, McCormick J. et al. Discovery of a periosteal stem cell mediating intramembranous bone formation. Nature 2018; 562 (7725): 133-139
  CrossrefPubMedGoogle Scholar
• 28 Lee H, Park J-B. Dimethyl sulfoxide leads to decreased osteogenic differentiation of stem cells derived from gingiva via Runx2 and collagen i expression. Eur J Dent 2019; 13 (02) 131-136
  Article in Thieme ConnectPubMedGoogle Scholar
• 29 Guo S, Guo W, Ding Y. et al. Comparative study of human dental follicle cell sheets and periodontal ligament cell sheets for periodontal tissue regeneration. Cell Transplant 2013; 22 (06) 1061-1073
  CrossrefPubMedGoogle Scholar
• 30 Nugraha AP, Ramadhani NF, Riawan W. et al. Gingival mesenchymal stem cells metabolite decreasing TRAP, NFATc1, and sclerostin expression in LPS-associated inflammatory osteolysis in vivo. Eur J Dent 2023; 17 (03) 881-888
  Article in Thieme ConnectPubMedGoogle Scholar
• 31 Morsczeck CO, Drees 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 (12) 1595-1601
  CrossrefPubMedGoogle Scholar
• 32 Pevsner-Fischer M, Morad V, Cohen-Sfady M. et al. Toll-like receptors and their ligands control mesenchymal stem cell functions. Blood 2007; 109 (04) 1422-1432
  CrossrefPubMedGoogle Scholar
• 33 Andrukhov O, Hong JSA, Andrukhova O, Blufstein A, Moritz A, Rausch-Fan X. Response of human periodontal ligament stem cells to IFN-γ and TLR-agonists. Sci Rep 2017; 7 (01) 12856 DOI: 10.1038/s41598-017-12480-7.
  CrossrefPubMedGoogle Scholar
• 34 Shin C, Kim M, Han JA. et al. Human periodontal ligament stem cells suppress T-cell proliferation via down-regulation of non-classical major histocompatibility complex-like glycoprotein CD1b on dendritic cells. J Periodontal Res 2017; 52 (01) 135-146
  CrossrefPubMedGoogle Scholar
• 35 Su WR, Zhang QZ, Shi SH, Nguyen AL, Le AD. Human gingiva-derived mesenchymal stromal cells attenuate contact hypersensitivity via prostaglandin E2-dependent mechanisms. Stem Cells 2011; 29 (11) 1849-1860
  CrossrefPubMedGoogle Scholar
• 36 Chen X, Yang B, Tian J. et al. Dental follicle stem cells ameliorate lipopolysaccharide-induced inflammation by secreting TGF-β3 and TSP-1 to elicit macrophage M2 polarization. Cell Physiol Biochem 2018; 51 (05) 2290-2308
  CrossrefPubMedGoogle Scholar
• 37 Chatzivasileiou K, Lux CA, Steinhoff G, Lang H. Dental follicle progenitor cells responses to Porphyromonas gingivalis LPS. J Cell Mol Med 2013; 17 (06) 766-773
  CrossrefPubMedGoogle Scholar
• 38 He F, Umrath F, von Ohle C, Reinert S, Alexander D. Analysis of the influence of jaw periosteal cells on macrophages phenotype using an innovative horizontal coculture system. Biomedicines 2021; 9 (12) 1753 DOI: 10.3390/biomedicines9121753.
  CrossrefPubMedGoogle Scholar
• 39 Queiroz A, Albuquerque-Souza E, Gasparoni LM. et al. Therapeutic potential of periodontal ligament stem cells. World J Stem Cells 2021; 13 (06) 605-618
  CrossrefPubMedGoogle Scholar
• 40 Ge S, Zhao N, Wang L, Liu H, Yang P. Effects of hydroxyapatite nanostructure on channel surface of porcine acellular dermal matrix scaffold on cell viability and osteogenic differentiation of human periodontal ligament stem cells. Int J Nanomedicine 2013; 8: 1887-1895
  CrossrefPubMedGoogle Scholar
• 41 Moshaverinia A, Xu X, Chen C. et al. Application of stem cells derived from the periodontal ligament or gingival tissue sources for tendon tissue regeneration. Biomaterials 2014; 35 (09) 2642-2650
  CrossrefPubMedGoogle Scholar
• 42 Yu B-H, Zhou Q, Wang Z-L. Periodontal ligament versus bone marrow mesenchymal stem cells in combination with Bio-Oss scaffolds for ectopic and in situ bone formation: a comparative study in the rat. J Biomater Appl 2014; 29 (02) 243-253
  CrossrefPubMedGoogle Scholar
• 43 Park S-Y, Kim K-H, Gwak E-H. et al. Ex vivo bone morphogenetic protein 2 gene delivery using periodontal ligament stem cells for enhanced re-osseointegration in the regenerative treatment of peri-implantitis. J Biomed Mater Res A 2015; 103 (01) 38-47
  CrossrefPubMedGoogle Scholar
• 44 Xu Q, Li B, Yuan L. et al. Combination of platelet-rich plasma within periodontal ligament stem cell sheets enhances cell differentiation and matrix production. J Tissue Eng Regen Med 2017; 11 (03) 627-636
  CrossrefPubMedGoogle Scholar
• 45 Iwasaki K, Komaki M, Yokoyama N. et al. Periodontal regeneration using periodontal ligament stem cell-transferred amnion. Tissue Eng Part A 2014; 20 (3-4): 693-704
  PubMedGoogle Scholar
• 46 Moshaverinia A, Chen C, Akiyama K. et al. Encapsulated dental-derived mesenchymal stem cells in an injectable and biodegradable scaffold for applications in bone tissue engineering. J Biomed Mater Res A 2013; 101 (11) 3285-3294
  CrossrefPubMedGoogle Scholar
• 47 Qiu J, Wang X, Zhou H. et al. Enhancement of periodontal tissue regeneration by conditioned media from gingiva-derived or periodontal ligament-derived mesenchymal stem cells: a comparative study in rats. Stem Cell Res Ther 2020; 11 (01) 42 DOI: 10.1186/s13287-019-1546-9.
  CrossrefPubMedGoogle Scholar
• 48 Nakao Y, Fukuda T, Zhang Q. et al. Exosomes from TNF-α-treated human gingiva-derived MSCs enhance M2 macrophage polarization and inhibit periodontal bone loss. Acta Biomater 2021; 122: 306-324
  CrossrefPubMedGoogle Scholar
• 49 Abdal-Wahab M, Abdel Ghaffar KA, Ezzatt OM, Hassan AAA, El Ansary MMS, Gamal AY. Regenerative potential of cultured gingival fibroblasts in treatment of periodontal intrabony defects (randomized clinical and biochemical trial). J Periodontal Res 2020; 55 (03) 441-452
  CrossrefPubMedGoogle Scholar
• 50 Hasani-Sadrabadi MM, Sarrion P, Pouraghaei S. et al. An engineered cell-laden adhesive hydrogel promotes craniofacial bone tissue regeneration in rats. Sci Transl Med 2020; 12 (534) eaay6853 DOI: 10.1126/scitranslmed.aay6853.
  CrossrefPubMedGoogle Scholar
• 51 Kandalam U, Kawai T, Ravindran G. et al. Predifferentiated gingival stem cell-induced bone regeneration in rat alveolar bone defect model. Tissue Eng Part A 2021; 27 (5-6): 424-436
  CrossrefPubMedGoogle Scholar
• 52 Diomede F, Gugliandolo A, Cardelli P. et al. Three-dimensional printed PLA scaffold and human gingival stem cell-derived extracellular vesicles: a new tool for bone defect repair. Stem Cell Res Ther 2018; 9 (01) 104 DOI: 10.1186/s13287-018-0850-0.
  CrossrefPubMedGoogle Scholar
• 53 Zhang Q, Nguyen PD, Shi S, Burrell JC, Cullen DK, Le AD. 3D bio-printed scaffold-free nerve constructs with human gingiva-derived mesenchymal stem cells promote rat facial nerve regeneration. Sci Rep 2018; 8 (01) 6634 DOI: 10.1038/s41598-018-24888-w.
  CrossrefPubMedGoogle Scholar
• 54 Honda MJ, Imaizumi M, Tsuchiya S, Morsczeck C. Dental follicle stem cells and tissue engineering. J Oral Sci 2010; 52 (04) 541-552
  CrossrefPubMedGoogle Scholar
• 55 Oshima M, Inoue K, Nakajima K. et al. Functional tooth restoration by next-generation bio-hybrid implant as a bio-hybrid artificial organ replacement therapy. Sci Rep 2014; 4: 6044 DOI: 10.1038/srep06044.
  CrossrefPubMedGoogle Scholar
• 56 Shinagawa-Ohama R, Mochizuki M, Tamaki Y, Suda N, Nakahara T. Heterogeneous human periodontal ligament-committed progenitor and stem cell populations exhibit a unique cementogenic property under in vitro and in vivo conditions. Stem Cells Dev 2017; 26 (09) 632-645
  CrossrefPubMedGoogle Scholar
• 57 Salgado CL, Barrias CC, Monteiro FJM. Clarifying the tooth-derived stem cells behavior in a 3D biomimetic scaffold for bone tissue engineering applications. Front Bioeng Biotechnol 2020; 8: 724 DOI: 10.3389/fbioe.2020.00724.
  CrossrefPubMedGoogle Scholar
• 58 Yang H, Li J, Hu Y. et al. Treated dentin matrix particles combined with dental follicle cell sheet stimulate periodontal regeneration. Dent Mater 2019; 35 (09) 1238-1253
  CrossrefPubMedGoogle Scholar
• 59 Tian Y, Bai D, Guo W. et al. Comparison of human dental follicle cells and human periodontal ligament cells for dentin tissue regeneration. Regen Med 2015; 10 (04) 461-479
  CrossrefPubMedGoogle Scholar
• 60 Guo W, Gong K, Shi H. et al. Dental follicle cells and treated dentin matrix scaffold for tissue engineering the tooth root. Biomaterials 2012; 33 (05) 1291-1302
  CrossrefPubMedGoogle Scholar
• 61 Tsuchiya S, Ohshima S, Yamakoshi Y, Simmer JP, Honda MJ. Osteogenic differentiation capacity of porcine dental follicle progenitor cells. Connect Tissue Res 2010; 51 (03) 197-207
  CrossrefPubMedGoogle Scholar
• 62 Kawase T, Okuda K, Kogami H. et al. Characterization of human cultured periosteal sheets expressing bone-forming potential: in vitro and in vivo animal studies. J Tissue Eng Regen Med 2009; 3 (03) 218-229
  CrossrefPubMedGoogle Scholar
• 63 Nagata M, Hoshina H, Li M. et al. A clinical study of alveolar bone tissue engineering with cultured autogenous periosteal cells: coordinated activation of bone formation and resorption. Bone 2012; 50 (05) 1123-1129
  CrossrefPubMedGoogle Scholar
• 64 Agata H, Asahina I, Yamazaki Y. et al. Effective bone engineering with periosteum-derived cells. J Dent Res 2007; 86 (01) 79-83
  CrossrefPubMedGoogle Scholar
• 65 Ueno T, Honda K, Hirata A. et al. Histological comparison of bone induced from autogenously grafted periosteum with bone induced from autogenously grafted bone marrow in the rat calvarial defect model. Acta Histochem 2008; 110 (03) 217-223
  CrossrefPubMedGoogle Scholar
• 66 Cicconetti A, Sacchetti B, Bartoli A. et al. Human maxillary tuberosity and jaw periosteum as sources of osteoprogenitor cells for tissue engineering. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007; 104 (05) 618.e1-618.e12
  CrossrefPubMedGoogle Scholar
• 67 Ge S, Zhao N, Wang L. et al. Bone repair by periodontal ligament stem cellseeded nanohydroxyapatite-chitosan scaffold. Int J Nanomedicine 2012; 7: 5405-5414
  CrossrefPubMedGoogle Scholar
• 68 Wang F, Yu M, Yan X. et al. Gingiva-derived mesenchymal stem cell-mediated therapeutic approach for bone tissue regeneration. Stem Cells Dev 2011; 20 (12) 2093-2102
  CrossrefPubMedGoogle Scholar
• 69 Al-Qadhi G, Aboushady I, Al-Sharabi N. The gingiva from the tissue surrounding the bone to the tissue regenerating the bone: a systematic review of the osteogenic capacity of gingival mesenchymal stem cells in preclinical studies. Stem Cells Int 2021; 2021: 6698100 DOI: 10.1155/2021/6698100.
  CrossrefPubMedGoogle Scholar
• 70 Diomede F, Rajan TS, D'Aurora M. et al. Stemness characteristics of periodontal ligament stem cells from donors and multiple sclerosis patients: a comparative study. Stem Cells Int 2017; 2017: 1606125 DOI: 10.1155/2017/1606125.
  CrossrefPubMedGoogle Scholar
• 71 Lee JS, An SY, Kwon IK, Heo JS. Transdifferentiation of human periodontal ligament stem cells into pancreatic cell lineage. Cell Biochem Funct 2014; 32 (07) 605-611
  CrossrefPubMedGoogle Scholar
• 72 Ulusoy C, Zibandeh N, Yıldırım S. et al. Dental follicle mesenchymal stem cell administration ameliorates muscle weakness in MuSK-immunized mice. J Neuroinflammation 2015; 12 (01) 231 DOI: 10.1186/s12974-015-0451-0.
  CrossrefPubMedGoogle Scholar
• 73 Shi HZ, Zeng JC, Shi SH, Giannakopoulos H, Zhang QZ, Le AD. Extracellular vesicles of GMSCs alleviate aging-related cell senescence. J Dent Res 2021; 100 (03) 283-292
  CrossrefPubMedGoogle Scholar
• 74 Subbarayan R, Barathidasan R, Raja STK. et al. Human gingival derived neuronal cells in the optimized caffeic acid hydrogel for hemitransection spinal cord injury model. J Cell Biochem 2020; 121 (03) 2077-2088
  CrossrefPubMedGoogle Scholar
• 75 Ansari S, Sarrion P, Hasani-Sadrabadi MM, Aghaloo T, Wu BM, Moshaverinia A. Regulation of the fate of dental-derived mesenchymal stem cells using engineered alginate-GelMA hydrogels. J Biomed Mater Res A 2017; 105 (11) 2957-2967
  CrossrefPubMedGoogle Scholar
• 76 Al-Qadhi G, Soliman M, Abou-Shady I, Rashed L. Gingival mesenchymal stem cells as an alternative source to bone marrow mesenchymal stem cells in regeneration of bone defects: in vivo study. Tissue Cell 2020; 63: 101325 DOI: 10.1016/j.tice.2019.101325.
  CrossrefPubMedGoogle Scholar
• 77 Ryu N-E, Lee S-H, Park H. Spheroid culture system methods and applications for mesenchymal stem cells. Cells 2019; 8 (12) E1620 DOI: 10.3390/cells8121620.
  CrossrefPubMedGoogle Scholar
• 78 Basu A, Rothermund K, Ahmed MN, Syed-Picard FN. Self-assembly of an organized cementum-periodontal ligament-like complex using scaffold-free tissue engineering. Front Physiol 2019; 10: 422 DOI: 10.3389/fphys.2019.00422.
  CrossrefPubMedGoogle Scholar
• 79 Hsu SH, Huang G-S, Feng F. Isolation of the multipotent MSC subpopulation from human gingival fibroblasts by culturing on chitosan membranes. Biomaterials 2012; 33 (09) 2642-2655
  CrossrefPubMedGoogle Scholar
• 80 Zhang Z, Shuai Y, Zhou F. et al. PDLSCs regulate angiogenesis of periodontal ligaments via VEGF transferred by exosomes in periodontitis. Int J Med Sci 2020; 17 (05) 558-567
  CrossrefPubMedGoogle Scholar
• 81 Pizzicannella J, Gugliandolo A, Orsini T. et al. Engineered extracellular vesicles from human periodontal-ligament stem cells increase VEGF/VEGFR2 expression during bone regeneration. Front Physiol 2019; 10: 512 DOI: 10.3389/fphys.2019.00512.
  CrossrefPubMedGoogle Scholar
• 82 Liu T, Hu W, Zou X. et al. Human periodontal ligament stem cell-derived exosomes promote bone regeneration by altering microRNA profiles. Stem Cells Int 2020; 2020: 8852307 DOI: 10.1155/2020/8852307.
  CrossrefPubMedGoogle Scholar
• 83 Ma L, Rao N, Jiang H. et al. Small extracellular vesicles from dental follicle stem cells provide biochemical cues for periodontal tissue regeneration. Stem Cell Res Ther 2022; 13 (01) 92 DOI: 10.1186/s13287-022-02767-6.
  CrossrefPubMedGoogle Scholar
• 84 Iwata T, Yamato M, Washio K. et al. Periodontal regeneration with autologous periodontal ligament-derived cell sheets - a safety and efficacy study in ten patients. Regen Ther 2018; 9: 38-44
  CrossrefPubMedGoogle Scholar
• 85 Nakahara T, Nakamura T, Kobayashi E. et al. In situ tissue engineering of periodontal tissues by seeding with periodontal ligament-derived cells. Tissue Eng 2004; 10 (3-4): 537-544
  CrossrefPubMedGoogle Scholar
• 86 Akbay A, Baran C, Günhan O, Ozmeriç N, Baloş K. Periodontal regenerative potential of autogenous periodontal ligament grafts in class II furcation defects. J Periodontol 2005; 76 (04) 595-604
  CrossrefPubMedGoogle Scholar
• 87 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 2016; 7: 33 DOI: 10.1186/s13287-016-0288-1.
  CrossrefPubMedGoogle Scholar
• 88 Kim D, Lee AE, Xu Q, Zhang Q, Le AD. Gingiva-derived mesenchymal stem cells: potential application in tissue engineering and regenerative medicine - a comprehensive review. Front Immunol 2021; 12: 667221 DOI: 10.3389/fimmu.2021.667221.
  CrossrefPubMedGoogle Scholar
• 89 Ponnaiyan D, Jegadeesan V. Comparison of phenotype and differentiation marker gene expression profiles in human dental pulp and bone marrow mesenchymal stem cells. Eur J Dent 2014; 8 (03) 307-313
  Article in Thieme ConnectPubMedGoogle Scholar