Gingiva as a new and the most accessible source of mesenchymal stem cells from the oral cavity to be used in regenerative therapies
Bartłomiej Górski 1Abstract
Since the discovery of bone marrow mesenchymal stem cells (BMMSCs), many researchers have focused their attention on new sources of mesenchymal stem cells (MSCs). Consequently, MSCs that display self-renewal capacity, multidifferentiation potential and immunomodulatory properties have been isolated from human oral tissues, including tooth, periodontal ligament, and gingiva. Oral MSCs involve dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), dental follicle stem cells (DFCs), stem cells from apical papilla (SCAP) and gingival stem cells (GMSCs). Current research on oral stem cells is expanding at an unprecedented rate. That being the case, a plethora of in vitro differentiation assays, immunodeficient animal transplantations and preclinical trials have demonstrated that these cells exhibit strong potential for both regenerative dentistry and medicine. Oral MSCs have proved their capability to repair cornea, dental pulp, periodontal, bone, cartilage, tendon, neural, muscle and endothelial tissues without neoplasm formation as well as to treat inflammatory diseases and immune disorders. This article describes the current understanding of oral MSCs and their prospective applications in cell-based therapy, tissue engineering and regenerative medicine. Special attention is placed on GMSCs as they are easily accessible and may be obtained in a convenient and minimally invasive way.
References
- 1. Akizuki T., Oda S., Komaki M., Tsuchioka H., Kawakatsu N., KikuchiA., Yamato M., Okano T., Ishikawa I.: Application of periodontalligament cell sheet for periodontal regeneration: a pilot study inbeagle dogs. J. Periodontal. Res., 2005; 40: 245-251
Google Scholar - 2. Arminán A., Gandia C., Bartual M., García-Verdugo J.M., LledóE., Mirabet V., Llop M., Barea J., Montero J.A., Sepúlveda P.: Cardiacdifferentiation is driven by NKX2.5 and GATA4 nuclear translocationin tissue-specific mesenchymal stem cells. Stem Cells Dev., 2009;18: 907-918
Google Scholar - 3. Arora V., Arora P., Munshi A.K.: Banking stem cells from humanexfoliated deciduous teeth (SHED): saving for the future. J. Clin. Pediatr.Dent., 2009; 33: 289-294
Google Scholar - 4. Arvidson K., Abdallah M., Applegate L.A., Baldini N., Cenni E.,Gomez-Barrena E., Granchi D., Kassem M., Konttinen Y.T., MustafaK., Pioletti D.P., Sillat T., Finne-Wistrand A.: Bone regeneration andstem cells. J. Cell. Mol. Med., 2011; 15: 718-746
Google Scholar - 5. Batouli S., Miura M., Brahim J., Tsutsui T.W., Fisher L.W., GronthosS., Robey P.G., Shi S.: Comparison of stem-cell-mediated osteogenesisand dentinogenesis. J. Dent. Res., 2003; 82: 976-981 6 Beltran S.R., Svoboda K.K., Kerns D.G., Sheth A., Prockop D.J.: Anti-inflammatoryprotein tumor necrosis factor-α-stimulated protein
Google Scholar - 6. (TSG-6) promotes early gingival wound healing: an in vivo study.J. Periodontol., 2015; 86: 62-71
Google Scholar - 7. Bianco P., Robey P.G., Simmons P.J.: Mesenchymal stem cells: revisitinghistory, concepts, and assays. Cell Stem Cell., 2008; 2: 313-319
Google Scholar - 8. Bosshardt D.D., Stadlinger B., Terheyden H.: Cell-to-cell communication– periodontal regeneration. Clin. Oral Implants Res.,2015; 26: 229-239
Google Scholar - 9. Catacchio I., Berardi S., Reale A., De Luisi A., Racanelli V., VaccaA., Ria R.: Evidence for bone marrow adult stem cell plasticity:properties, molecular mechanisms, negative aspects, and clinicalapplications of hematopoietic and mesenchymal stem cells transdiferentiation.Stem Cells Int., 2013; 2013: 589139
Google Scholar - 10. Chen M., Su W., Lin X., Guo Z., Wang J., Zhang Q., Brand D., RyffelB., Huang J., Liu Z., He X., Le A.D., Zheng S.G.: Adoptive transfer of humangingiva-derived mesenchymal stem cells ameliorates colagen–induced arthritis via suppresion Th1 and Th17 and enhancement ofregulatory T cell differeniation. Arthritis Rheum., 2013; 65: 1181-1193
Google Scholar - 11. Choi J.K., Hwang H.I., Jang Y.J.: The efficiency of the in vitroosteo/dentinogenic differentiation of human dental pulp cells, periodontalligament cells and gingival fibroblasts. Int. J. Mol. Med.,2015; 35: 161-168
Google Scholar - 12. Cordeiro M.M., Dong Z., Kaneko T., Zhang Z., Miyazawa M., ShiS., Smith A.J., Nör J.E.: Dental pulp tissue engineering with stemcells from exfoliated deciduous teeth. J. Endod., 2008; 34: 962-969
Google Scholar - 13. Crisan M., Corselli M., Chen C.W., Péault B.: Multilineage stem cellsin the adult: a perivascular legacy? Organogenesis, 2011; 7: 101-104
Google Scholar - 14. d’Aquino R., De Rosa A., Lanza V., Tirino V., Laino L., GrazianoA., Desiderio V., Laino G., Papaccio G.: Human mandible bone defectrepair by the grafting of dental pulp stem/progenitor cells and collagensponge biocomplexes. Eur. Cell Mater., 2009; 18: 75-83
Google Scholar - 15. d’Aquino R., Tirino V., Desiderio V., Studer M., De Angelis G.C.,Laino L., De Rosa A., Di Nucci D., Martino S., Paino F., SampaolesiM., Papaccio G.: Human neural crest-derived postnatal cells exhibitremarkable embryonic attributes either in vitro or in vivo. Eur. CellMater., 2011; 21: 304-316
Google Scholar - 16. de Almeida F.M., Marques S.A., Ramalho B.S., Rodrigues R.F.,Cadilhe D.V., Furtado D., Kerkis I., Pereira L.V., Rehen S.K., MartinezA.M.: Human dental pulp cells: a new source of cell therapy ina mouse model of compressive spinal cord injury. J. Neurotrauma.2011; 28: 1939-1949
Google Scholar - 17. Ding G., Liu Y., An Y., Zhang C., Shi S., Wang W., Wang S.: Suppressionof T cell proliferation by root apical papilla stem cells invitro. Cells Tissues Organs, 2010; 191: 357-364
Google Scholar - 18. Ding G., Liu Y., Wang W., Wei F., Liu D., Fan Z., An Y., Zhang C.,Wang S.: Allogeneic periodontal ligament stem cell therapy for periodontitisin swine. Stem Cells, 2010; 28: 1829-1838
Google Scholar - 19. Ding G., Niu J., Wei F.: Current understanding of orofacial tissuederived mesenchymal stem cells: an immunological perspective.Histol. Histopathol., 2015; 30: 255-265
Google Scholar - 20. Dominici M., Le Blanc K., Mueller I., Slaper-Cortenbach I., MariniF., Krause D., Deans R., Keating A., Prockop D.J., Horowitz E.: Minimalcriteria for defining multipotent mesenchymal stromal cells. TheInternational Society for Cellular Therapy position statement. Cytotherapy,2006; 8: 315-317
Google Scholar - 21. Eleuterio E., Trubiani O., Sulpizio M., Di Giuseppe F., PierdomenicoL., Marchisio M., Giancola R., Giammaria G., Miscia S., Caputi S., DiIlio C., Angelucci S.: Proteome of human stem cells from periodontalligament and dental pulp. PLoS One, 2013; 8: e71101
Google Scholar - 22. El-Bialy T., Alhadlaq A., Wong B., Kucharski C.: Ultrasound effecton neural differentiation of gingival stem/progenitor cells. Ann.Biomed. Eng., 2014; 42: 1406-1412
Google Scholar - 23. El-Sayed K.M., Paris S., Graetz C., Kassem N., Mekhemar M.,Ungefroren H., Fändrich F., Dörfer C.: Isolation and characterisationof human gingival margin-derived STRO-1/MACS+ and MACS – cellpopulations. Int. J. Oral Sci., 2015; 7: 80-88
Google Scholar - 24. Eslami A., Gallant-Behm C.L., Hart D.A., Wiebe C., HonardoustD., Gardner H., Häkkinen L., Larjava H.S.: Epression of integrin αvβ6and TGF-β in scarless vs. scar-forming wound healing. J. Histochem.Cytochem., 2009; 57: 543-557
Google Scholar - 25. Favzy El-Sayed K.M., Paris S., Becker S.T., Neuschl M., De BuhrW., Sälzer S., Wulff A., Elrefai M., Darhous M.S., El-Masry M., WiltfangJ., Dörfer C.E.: Periodontal regeneration employing gingivalmargin-derived stem/progenitor cells: an animal study. J. Clin. Periodontol.;2012; 39: 861-870
Google Scholar - 26. Feng F., Akiyama K., Liu Y., Yamaza T., Wang T.M., Chen J.H., WangB.B., Huang G.T., Wang S., Shi S.: Utility of PDL progenitors for in vivotissue regeneration: a report of 3 cases. Oral Dis., 2010; 16: 20-28
Google Scholar - 27. Ferré F.C., Larjava H., Loison-Robert L.S., Berbar T., Owen G.R.,Berdal A., Chérifi H., Gogly B., Häkkinen L., Fournier B.P.: Formationof cartilage and synovial tissue by human gingival stem cells. StemCells Dev., 2014; 23: 2895-2907
Google Scholar - 28. Ferretti C., Borsari V., Falconi M., Gigante A., Lazzarini R., FiniM., Di Primio R., Mattioli-Belmonte M.: Human periosteum-derivedstem cells for tissue engineering applications: the role of VEGF. Stem.Cell. Rev., 2012; 8: 882-890
Google Scholar - 29. Fournier B.P., Ferre F.C., Couty L., Lataillade J.J., Gourven M.,Naveau A., Coulomb B., Lafont A., Gogly B.: Multipotent progrenitorcells in gingival connective tissue. Tissue Eng. Part A, 2010; 16:2891-2899
Google Scholar - 30. Galler K.M., D’Souza R.N., Federlin M., Cavender A.C., HartgerinkJ.D., Hecker S., Schmalz G.: Dentin conditioning codeterminescell fate in regenerative endodontics. J. Endod., 2011; 37: 1536-1541
Google Scholar - 31. Gandia C., Arminan A., Garcia-Verdugo J.M., Lledó E., Ruiz A.,Miñana M.D., Sanchez-Torrijos J., Payá R., Mirabet V., Carbonell–Uberos F., Llop M., Montero J.A., Sepúlveda P.: Human dental pulpstem cells improve left ventricular function, induce angiogenesis,and reduct infarct size in rats with acute myocardial infarction. StemCells, 2008; 26: 638-645
Google Scholar - 32. Gao Y., Zhao G., Li D., Chen X., Pang J., Ke J.: Isolation and multipledifferentiation potential assessment of human gingival mesenchymalstem cells. Int. J. Mol. Sci., 2014; 15: 20982-20996
Google Scholar - 33. Ge S., Mrozik K.M., Menicanin D., Gronthos S., Bartold P.M.:Isolation and characterization of mesenchymal stem cell-like cellsfrom healthy and inflamed gingival tissue: potential use for clinicaltherapy. Regen. Med., 2012; 7: 819-832
Google Scholar - 34. Gomes J.A., Geraldes Monteiro B., Melo G.B., Smith R.L., CavenaghiPereira da Silva M., Lizier N.F., Kerkis A., Cerruti H., Kerkis I.:Corneal reconstruction with tissue-engineered cell sheets composedof human immature dental pulp stem cells. Invest. Ophthalmol. Vis.Sci., 2010; 51: 1408-1414
Google Scholar - 35. Govindasamy V., Ronald V.S., Abdullah A.N., Nathan K.R., AbAziz Z.A., Abdullah M., Musa S., Kasim N.H., Bhonde R.R.: Differentiationof dental pulp stem cells into islet-like aggregates. J. Dent.Res., 2011; 90: 646-652
Google Scholar - 36. Gronthos S., Mankani M., Brahim J., Robey P.G., Shi S.: Postnatalhuman dental pulp stem cells (DPSCs) in vitro and in vivo. Proc. Natl.Acad. Sci. USA, 2000; 97: 13625-13630
Google Scholar - 37. Guo W., Chen L., Gong K., Ding B., Duan Y., Jin Y.: Heterogeneousdental follicle cells and the regeneration of complex periodontaltissue. Tissue Eng. Part A, 2012; 18: 459-470
Google Scholar - 38. Han C., Yang Z., Zhou W., Jin F., Song Y., Wang Y., Huo N., ChenL., Qian H., Hou R., Duan Y., Jin Y.: Periapical follicle stem cell: a promisingcandidate for cementum/periodontal ligament regenerationand bio-root engineering. Stem Cells Dev., 2010; 19: 1405-1414
Google Scholar - 39. Hilkens P., Gervois P., Fanton Y., Vanormelingen J., Martens W.,Struys T., Politis C., Lambrichts I., Bronckaers A.: Effect of isolationmethodology on stem cell properties and multilineage differentiationpotential of human dental pulp stem cells. Cell Tissue Res.,2013; 353: 65-78
Google Scholar - 40. Huang G.T., Sonoyama W., Liu Y., Liu H., Wang S., Shi S.: Thehidden treasure in apical papilla: the potential role in pulp/dentinregeneration and bioroot engineering. J. Endod., 2008; 34: 645-651
Google Scholar - 41. Huang G.T., Yamaza T., Shea L.D., Djouad F., Kuhn N.Z., TuanR.S., Shi S.: Stem/progenitor cell-mediated de novo regeneration ofdental pulp with newly deposited continuous layer of dentin in anin vivo model. Tissue Eng. Part A, 2010; 16: 605-615
Google Scholar - 42. Iohara K., Murakami M., Takeuchi N., Osako Y., Ito M., IshizakaR., Utunomiya S., Nakamura H., Matsushita K., Nakashima M.: A novelcombinatorial therapy with pulp stem cells and granulocytecolony-stimulating factor for total pulp regeneration. Stem CellsTransl. Med., 2013; 2: 521-533
Google Scholar - 43. Ishkitiev N., Calenic B., Aoyama I., Li H., Yaegaki K., Imai T.: Hydrogensulfide increases hepatic differentiation in tooth-pulp stemcells. J. Breath Res., 2012; 6: 017103
Google Scholar - 44. Ishkitiev N., Yaegaki K., Calenic B., Nakahara T., Ishikawa H., MitievV., Haapasalo M.: Deciduous and permanent dental pulp mesenchymalcells acquire hepatic morphologic and functional featuresin vitro. J. Endod., 2010; 36: 469-474
Google Scholar - 45. Ishkitiev N., Yaegaki K., Kozhuharova A., Tanaka T., Okada M.,Mitev V., Fukuda M., Imai T.: Pancreatic differentiation of humandental pulp CD117+ stem cells. Regen. Med., 2013; 8: 597-612
Google Scholar - 46. Jamal M., Chogle S., Goodis H., Karam S.M.: Dental stem cells andtheir potential role in regenerative medicine. J. Med. Sci., 2011; 4: 53-61
Google Scholar - 47. Jiang C.M., Liu J., Zhao J.Y., Xiao L., An S., Gou Y.C., Quan H.X.,Cheng Q., Zhang Y.L., He W., Wang Y.T., Yu W.J., Huang Y.F., Yi Y.T.,Chen Y., Wang J.: Effects of hypoxia on the immunomodulatory propertiesof human gingiva-derived mesenchymal stem cells. J. Dent.Res., 2015; 94: 69-77
Google Scholar - 48. Jin S.H., Lee J.E., Yun J.H., Kim I., Ko Y., Park J.B.: Isolation andcharacterization of human mesenchymal stem cells from gingivalconnective tissue. J. Periodontal Res., 2015; 50: 461-467
Google Scholar - 49. Kaltschmidt B., Kaltschmidt C., Widera D.: Adult craniofacialstem cells: sources and relation to the neural crest. Stem Cell Rev.2012; 8: 658-671
Google Scholar - 50. Kawase T., Okuda K., Kogami H., Nakayama H., Nagata M., SatoT., Wolff L.F., Yoshie H.: Human periosteum-derived cells combinedwith superporous hydroxyapatite blocks used as an osteogenicbone substitute for periodontal regenerative therapy: an animal implantationstudy using nude mice. J. Periodontol., 2010; 81: 420-427
Google Scholar - 51. Kerkis I., Ambrosio C.E., Kerkis A., Martins D.S., Zucconi E., FonsecaS.A., Cabral R.M., Maranduba C.M., Gaiad T.P., Morini A.C., VieiraN.M., Brolio M.P., Sant’Anna O.A., Miglino M.A., Zatz M.: Earlytransplantation of human immature dental pulp stem cells frombaby teeth to golden retriever muscular dystrophy (GRMD) dogs:local or systemic. J. Transl. Med., 2008; 6: 35
Google Scholar - 52. Kerkis I., Kerkis A., Dozortsev D., Stukart-Parsons G.C., GomesMassironi S.M., Pereira L.V., Caplan A.I., Cerruti H.F.: Isolation andcharacterization of a population of immature dental pulp stem cellsexpressing OCT-4 and other embryonic stem cell markers. Cells TissuesOrgans, 2006; 184: 105-116
Google Scholar - 53. Khorsand A., Eslaminejad M.B., Arabsolghar M., Paknejad M.,Ghaedi B., Rokn A.R., Moslemi N., Nazarian H., Jahangir S.: Autologousdental pulp stem cells in regeneration of defect created in canineperiodontal tissue. J. Oral Implantol., 2013; 39: 433-443
Google Scholar - 54. Király M., Kádár K., Horváthy D.B., Nardai P., Rácz G.Z., LaczaZ., Varga G., Gerber G.: Integration of neuronally predifferentiatedhuman dental pulp stem cells into rat brain in vivo. Neurochem.Int., 2011; 59: 371-381
Google Scholar - 55. Kuçi S., Kuçi Z., Latifi-Pupovci H., Niethammer D., HandgretingerR., Schumm M., Bruchelt G., Bader P., Klingebiel T.: Adult stem cellsas an alternative source of multipotential (pluripotential) cells inregenerative medicine. Curr. Stem Cell Res. Ther., 2009; 4: 107-117
Google Scholar - 56. Lee J.H., Lee D.S., Choung H.W., Shon W.J., Seo B.M., Lee E.H.,Cho J.Y., Park J.C.: Odontogenic differentiation of human dental pulpstem cells induced by preameloblast-derived factors. Biomaterials,2011; 32: 9696-9706
Google Scholar - 57. Lee T.H., Kim W.T., Ryu C.J., Jang Y.J.: Optimization of treatmentwith recombinant FGF-2 for proliferation and differentiation ofhuman dental stem cells, mesenchymal stem cells, and osteoblasts.Biochem. Cell Biol., 2015; 93: 298-305
Google Scholar - 58. Li N., Liu N., Zhou J., Tang L., Ding B., Duan Y., Jin Y.: Inflammatoryenvironment induces gingival tissue-specific mesenchymalstem cells to differentiate towards a pro-fibrotic phenotype. Biol.Cell., 2013; 105: 261-275
Google Scholar - 59. Li Z., Jiang C.M., An S., Cheng Q., Huang Y.F., Wang Y.T., Gou Y.C.,Xiao L., Yu W.J., Wang J.: Immunomodulatory properties of dentaltissue-derived mesenchymal stem cells. Oral Dis., 2014; 20: 25-34
Google Scholar - 60. Liu D., Xu J., Liu O., Fan Z., Liu Y., Wang F., Ding G., Wei F., ZhangC., Wang S.: Mesenchymal stem cells derived from inflamed periodontalligaments exhibit impaired immunomodulation. J. Clin. Periodontol.,2012; 39: 1174-1182
Google Scholar - 61. Liu O., Xu J., Ding G., Liu D., Fan Z., Zhang C., Chen W., Ding Y.,Tang Z., Wang S.: Periodontal ligament stem cells regulate B lymphocytefunction via programmed cell death protein 1. Stem Cells,2013; 31: 1371-1382
Google Scholar - 62. Marynka-Kalmani K., Treves S., Yafee M., Rachima H., Gafni Y.,Cohen M.A., Pitaru S.: The lamina propria of adult human oral mucosaharbors a novel stem cell population. Stem Cells, 2010; 28: 984-995
Google Scholar - 63. Matsubara T., Suardita K., Ishii M., Sugiyama M., Igarashi A., OdaR., Nishimura M., Saito M., Nakagawa K., Yamanaka K., Miyazaki K.,Shimizu M., Bhawal U.K., Tsuji K., Nakamura K. i wsp.: Alveolar bonemarrow as a cell source for regenerative medicine: differences betweenalveolar and iliac bone marrow stromal cells. J. Bone Miner.Res., 2005; 20: 399-409
Google Scholar - 64. Mead B., Logan A., Berry M., Leadbeater W., Scheven B.A.: Intraviterallytransplanted dental pulp stem cells promote neuroprotectionand axon regeneration of retinal ganglion cells after optic nerveinjury. Invest. Ophthalmol. Vis. Sci., 2013; 54: 7544-7556
Google Scholar - 65. Mitrano T., Grob M.S., Carrión F., Nova-Lamperti E., Luz P.A.,Fierro F.S., Quintero A., Chaparro A., Sanz A.: Culture and characterizationof mesenchymal stem cells from human gingival tissue. J.Periodontol., 2010; 81: 917-925
Google Scholar - 66. Miura M., Gronthos S., Zhao M., Lu B., Fisher L.W., Robey P.G., ShiS.: SHED: stem cells from human exfoliated deciduous teeth. Proc.Natl. Acad. Sci. USA, 2003; 100: 5807-5812
Google Scholar - 67. Morszczeck C., Götz W., Schierholz J., Zeilhofer F., Kühn U., MöhlC., Sippel C., Hoffmann K.H.: Isolation of precursor cells (PCs) fromhuman dental follicle of wisdom teeth. Matrix Biol., 2005; 24: 155-165
Google Scholar - 68. Morszczeck C., Völlner F., Saugspier M., Brandl C., Reichert T.E., DriemelO., Schmalz G.: Comparison of human dental follicle cells (DFCs) andstem cells from human exfoliated deciduous teeth (SHED) after neuraldifferentiation in vitro. Clin. Oral Investig., 2010; 14: 433-440
Google Scholar - 69. Moshaverinia A., Chen C., Xu X., Akiyama K., Ansari S., ZadehH.H., Shi S.: Bone regeneration potential of stem cells derived fromperiodontal ligament or gingival tissue sources encapsualated inRGD-modified alginate scaffold. Tisse Eng. Part A, 2014; 20: 611-621
Google Scholar - 70. Moshaverinia A., Xu X., Chen C., Akiyama K., Snead M.L., Shi S.:Dental mesenchymal stem cells encapsulated in an alginate hydrogelco-delivery microencapsulation system for cartilage regeneration.Acta Biomater., 2013; 9: 9343-9350
Google Scholar - 71. Murakami M., Horibe H., Iohara K., Hayashi Y., Osako Y., TakeiY., Nakata K., Motoyama N., Kurita K., Nakashima M.: The useof granulocyte-colony stimulating factor induced mobilization forisolation of dental pulp stem cells with high regenerative potential.Biomaterials, 2013; 34: 9036-9047
Google Scholar - 72. Nozaki T., Ohura K.: Regulation of miRNA during direct reprogrammingof dental pulp cells to insulin-producing cells. Biochem.Biophys. Res. Commun., 2014; 444: 195-198
Google Scholar - 73. Okada M., Ishkitiev N., Yaegaki K., Imai T., Tanaka T., Fukuda M.,Ono S., Haapasalo M.: Hydrogen sulfide increases hepatic differentiationof human tooth-pulp stem cells compared wth human bone–marrow stem cells. Int. Endod. J., 2014; 47: 1142-1150
Google Scholar - 74. Pierdomenico L., Bonsi L, Calvitti M., Rondelli D., Arpinati M.,Chirumbolo G., Becchetti E., Marchionni C., Alviano F., Fossati V.,Staffolani N., Franchina M., Grossi A., Bagnara G.P.: Multipotentmesenchymal stem cells with immunosuppressive activity can beeasily isolated from dental pulp. Transplantation, 2005; 80: 836-842
Google Scholar - 75. Rizk A., Rabie A.B.: Human dental pulp stem cells expressingtransforming growth factor β3 transgene for cartilage-like tissueengineering. Cytotherapy, 2013; 15: 712-725
Google Scholar - 76. Sakai K., Yamamoto A., Matsubara K., Nakamura S., Naruse M.,Yamagata M., Sakamoto K., Tauchi R., Wakao N., Imagama S., HibiH., Kadomatsu K., Ishiguro N., Ueda M.: Human dental pulp-derivedstem cells promote locomotor recovery after complete transectionof the rat spinal cord by multiple neuro-regenerative mechanisms.J. Clin. Invest., 2012; 122: 80-90
Google Scholar - 77. Samee M., Kasugai S., Kondo H., Ohya K., Shimokawa H., KurodaS.: Bone morphogenetic protein-2 (BMP-2) and vascular endothelialgrowth factor (VEGF) transfection to human periosteal cells enhancesosteoblasts differentiation and bone formation. J. Pharamacol.Sci., 2008; 108: 18-31
Google Scholar - 78. Seo B.M., Miura M., Gronthos S., Bartold P.M., Batouli S., BrahimJ., Young M., Robey P.G., Wang C.Y., Shi S.: Investigation of multipotentpostnatal stem cells from human periodontal ligament. Lancet,2004; 364: 149-155
Google Scholar - 79. Seo B.M., Sonoyama W., Yamaza T., Coppe C., Kikuiri T., AkiyamaK., Lee J.S., Shi S.: SHED repair critical-size calvarial defects in mice.Oral. Dis., 2008; 14: 428-434
Google Scholar - 80. Song M., Kim H., Choi Y., Kim K., Chung C.: Skeletal myogenicdifferentiation of human periodontal ligament stromal cells isolatedfrom orthodontically extracted premolars. Korean J. Orthod.,2012; 42: 249-254
Google Scholar - 81. Sonoyama W., Liu Y., Fang D., Yamaza T., Seo B.M., Zhang C.,Liu H., Gronthos S., Wang C.Y., Wang S., Shi S.: Mesenchymal stemcell-mediated functional tooth regeneration in swine. PLoS One,2006; 1: e79
Google Scholar - 82. Sonoyama W., Liu Y., Yamaza T., Tuan R.S., Wang S., Shi S., HuangG.T.: Characterization of the apical papilla and its residing stemcells from human immature permanent teeth: a pilot study. J. Endod.,2008; 34: 166-171
Google Scholar - 83. Stevens A., Zuliani T., Olejnik C., LeRoy H., Obriot H., Kerr-ConteJ., Formstecher P., Bailliez Y., Polakowska R.R.: Human dental pulpstem cells differentiate into neural crest – derived melanocytes andhave label-retaining and sphere-forming abiliteis. Stem Cells Dev.,2008; 17: 1175-1184
Google Scholar - 84. Su W.R., Zhang Q.Z., Shi S.H., Nguyen A.L., Le A.D.: Human gingiva-derivedmesenchymal stromal cells attanuate contact hypersensitivityvia prostaglandin E2-dependent mechanisms. Stem Cells,2011; 29: 1849-1860
Google Scholar - 85. Taghipour Z., Karbalaie K., Kiani A., Niapour A., Bahramian H.,Nasr-Esfahani M.H., Baharvand H.: Transplantation of undifferentiatedand induced human exfoliated deciduous teeth-derived stemcells promote functional recovery of rat spinal cord contusion injurymodel. Stem Cells Dev., 2012; 21: 1794-1802
Google Scholar - 86. Tamaki Y., Nakahara T., Ishikawa H., Sato S.: In vitro analysis ofmesenchymal stem cells derived from human teeth and bone marrow.Odontology, 2013; 101: 121-132
Google Scholar - 87. Tang L., Li N., Xie H., Jin Y.: Characterization of mesenchymalstem cells from human normal and hyperplastic gingiva. J. CellPhysiol., 2011; 226: 832-842
Google Scholar - 88. Tomar G.B., Srivastava R.K., Gupta N., Barhanpurkar A.P., PoteS.T., Jhaveri H.M., Mishra G.C., Wani M.R.: Human gingiva-derivedmesenchymal stem cells are superior to bone marrow-derived mesenchymalstem cells for cell therapy in regenerative medicine. Biochem.Biophys. Res. Commun., 2010; 393: 377-383
Google Scholar - 89. Tomic S., Djokic J., Vasilijic S., Vucevic D., Todorovic V., Supic G.,Colic M.: Immunomodulatory properties of mesenchymal stem cellsderived from dental pulp and dental follicle are susceptible to activationby toll-like receptor agonists. Stem Cells Dev., 2011; 20: 695-708
Google Scholar - 90. Tuan R.S., Boland G., Tuli R.: Adult mesenchymal stem cells andcell-based tissue engineering. Arthritis Res. Ther., 2003, 5: 32-45
Google Scholar - 91. Wada N., Menicanin D., Shi S., Bartold P.M., Gronthos S.: Immunomodulatoryproperties of human periodontal ligament stemcells. J. Cell Physiol., 2009; 219: 667-676
Google Scholar - 92. Wang F., Yu M., Yan X., Wen Y., Zeng Q., Yue W., Yang P., Pei X.: Gingiva-derivedmesenchymal stem cell-mediated therapeutic approachfor bone tissue regeneration. Stem Cells Dev., 2011; 20: 2093-2102
Google Scholar - 93. Wang J., Wang X., Sun Z., Wang X., Yang H., Shi S., Wang S.: Stemcells from human-exfoliated deciduous teeth can differentiate intodopaminergic neuron-like cells. Stem Cells Dev., 2010; 19: 1375-1383
Google Scholar - 94. Wang J., Wei X., Ling J., Huang Y., Gong Q., Huo Y.: Identificationand characterization of side population cells from adult humandental pulp after ischemic culture. J. Endod., 2012; 38: 1489-1497
Google Scholar - 95. Wei F., Qu C. Song T., Ding G., Fan Z., Liu D., Liu Y., Zhang C., ShiS., Wang S.: Vitamin C treatment promotes mesenchymal stem cellsheet formation and tissue regeneration by elevating telomeraseactivity. J. Cell Physiol., 2012; 227: 3216-3224
Google Scholar - 96. Wei F., Song T., Ding G., Xu J., Liu Y., Liu D., Fan Z., Zhang C.,Shi S., Wang S.: Functional tooth restoration by allogenic mesenchymalstem cell-based bio-root regeneration in swine. Stem CellsDev., 2013; 22: 1752-1762
Google Scholar - 97. Wu S.M., Chiu H.C., Chin Y.T., Lin H.Y., Chiang C.Y., Tu H.P., FuM.M., Fu E.: Effects of enamel matrix derivative on the proliferationand osteogenic differentiation of human gingival mesenchymal stemcells. Stem Cell Res. Ther., 2014; 5: 52
Google Scholar - 98. Xia L., Peng R., Leng W., Jia R., Zeng X., Yang X., Fan M.: TRAILexpressinggingival-derived mesenchymal stem cells inhibit tumorigenesisof tongue squamous cell carcionoma. J. Dent. Res., 2015;94: 219-228
Google Scholar - 99. Xiao L., Tsutsui T.: Characterization of human dental pulp cellsderivedspheroids in serum-free medium: stem cells in the core. J.Cell. Biochem., 2013; 114: 2624-2636
Google Scholar - 100. Xu Q.C., Wang Z.G., Ji Q.X., Yu X.B., Xu X.Y., Yuan C.Q., DengJ., Yang P.S.: Systematically transplanted human gingiva-derivedmesenchymal stem cells contributing to bone tissue regeneration.Int. J. Clin. Exp. Pathol., 2014; 7: 4922-4929
Google Scholar - 101. Xu X., Chen C., Akiyama K., Chai Y., Le A.D., Wang Z., Shi S.:Gingivae contain neural-crest – and mesoderm-derived mesenchymalstem cells. J. Dent. Res., 2013; 92: 825-832
Google Scholar - 102. Yamagata M., Yamamoto A., Kako E., Kaneko N., Matsubara K.,Sakai K., Sawamoto K., Ueda M.: Human dental pulp-derived stemcells protect against hypoxic-ischemic brain injury in neonatal mice.Stroke, 2013; 44: 551-554
Google Scholar - 103. Yamaza T., Kentaro A., Chen C., Liu Y., Shi Y., Gronthos S., WangS., Shi S.: Immunomodulatory properties of stem cells from humanexfoliated deciduous teeth. Stem Cell Res. Ther., 2010; 1: 5
Google Scholar - 104. Yang B., Chen G., Li J., Zou Q., Xie D., Chen Y., Wang H., ZhengX., Long J., Tang W., Guo W., Tian W.: Tooth root regeneration usingdental follicle cell-sheets in combination with a dentin matrix-basedscaffold. Biomaterials, 2012; 33: 2449-2461
Google Scholar - 105. Yang H., Gao L.N., An Y., Hu C.H., Jin F., Zhou J., Jin Y., ChenF.M.: Comparison of mesenchymal stem cells derived from gingivaltissue and periodontal ligament in different incubation conditions.Biomaterials, 2013; 34: 7033-7047
Google Scholar - 106. Yang R., Chen M., Lee C.H., Yoon R., Lal S., Mao J.J.: Clones ofectopic stem cells in the regeneration of muscle defects in vivo. PLoSOne, 2010; 5: e13547
Google Scholar - 107. Yu X., Ge S., Chen S., Xu Q., Zhang J., Guo H., Yang P.: Human gingiva-derivedmesenchymal stromal cells contribute to periodontalregeneration in beagle dogs. Cells Tissues Organs, 2013; 198: 428-437
Google Scholar - 108. Zhang L., Ye J.S., Decot V., Stoltz J.F., De Isla N.: Research on stemcells as candidates to be differentiatetd into hepatocytes. Biomed.Mater. Eng., 2012; 22: 105-111
Google Scholar - 109. Zhang Q., Nguyen A.L., Shi S., Hill C., Wilder-Smith P., KrasievaT.B., Le A.D.: Three-dimensional spheroid culture of human gingivaderivedmesenchymal stem cells enhances mitigation of chemotherapy-inducedoral mucositis. Stem Cells Dev., 2012; 21: 937-947
Google Scholar - 110. Zhang Q., Shi S., Liu Y., Uyanne J., Shi Y., Shi S., Le A.D.: Mesenchymalstem cells derived from human gingiva are capable of immunomodulatoryfunctions and ameliorate inflammation-related tissuedestruction in experimental colitis. J. Immunol., 2009; 183: 7787-7798
Google Scholar - 111. Zhang Q.Z., Su W.R., Shi S.H., Wilder-Smith P., Xiang A.P., WongA., Nguyen A.L., Kwon C.W., Le A.D.: Human gingiva-derived mesenchymalstem cells elicit polarization of m2 macrophages and enhancecutaneous wound healing. Stem Cells, 2010; 28: 1856-1868
Google Scholar - 112. Zhang W., Walboomers X.F., Van Kuppevelt T.H., Daamen W.F.,Van Damme P.A., Bian Z., Jansen J.A.: In vivo evaluation of humandental pulp stem cells differentiated towards multiple lineages. J.Tissue Eng. Regen. Med., 2008; 2: 117-125
Google Scholar - 113. Zhao Y. Wang L., Jin Y., Shi S.: Fas ligand regulates the immunomodulatoryproperties of dental pulp stem cells. J. Dent. Res.,2012; 91: 948-954
Google Scholar - 114. Zorin V.L., Komlev V.S., Zorina A.I., Khromova N.V., SolovievaE.V., Fedotov A.Y., Eremin I.I., Kopnin P.B.: Octacalcium phosphate ceramicscombined with gingiva-derived stromal cells for engineeredfunctional bone grafts. Biomed. Mater., 2014; 9: 055005
Google Scholar