Dental Mesenchymal Stem Cell: Its role in tooth development, types, surface antigens and differentiation potential

Yohanna Feter, Nadhia Sari Afiana, Jessica Nathalia Chandra, Kharima Abdullah, Jasmine Shafira, Ferry Sandra


Reciprocal interaction between oral ectodermal epithelial cells and mesenchymal stem cells (MSCs)-derived from the cranial neural crest starts the teeth development. The role of dental MSCs continues throughout life. The dental MSCs do not only play a role in tooth development but also in tooth homeostasis and repair. There are many kinds of dental MSCs, such as dental pulp stem cell (DPSC), stem cell from apical papilla (SCAP), stem cell from exfoliated deciduous teeth (SHED), periodontal ligament stem cell (PDLSC) and stem cell from dental follicle (DFSC). Aligned with the proposed criteria by the International Society for Cellular Therapy (ISCT), dental MSCs are adherent cells and like other MSCs, dental tissue MSCs are capable of giving rise to cell lineages such as osteo/odontogenic, adipogenic, and neurogenic. Various surface antigens of dental MSCs were reported, however, mostly typical antigens suggested by ISCT were fulfilled. Surface antigens from each dental MSCs (DPSC, SCAP, SHED, PDLSC and DFSC) are being described in the current report.

Keywords: dental stem cells, mesenchymal stem cells, tissue regeneration, DPSC, SCAP, SHED, PDLSC, DFSC

Full Text:



Volponi AA, Pang Y, Sharpe PT. Stem cell-based biological tooth repair and regeneration. Trends Cell Biol. 2010; 20(12): 715-22. CrossRef

Sandra F, Sudiono S, Binartha CTO, Chouw A, Djamil MS. Growth and Osteogenic Differentiation of CD117+ Dental Pulp and Periodontal Ligament Cells. Indones Biomed J. 2017; 9(2): 78-83. CrossRef

Ledesma-Martínez E, Mendoza-Núñez V, Santiago-Osorio E. Mesenchymal Stem Cells Derived from Dental Pulp: A Review. Stem Cells Int. 2016; 2016: 4709572. doi: 10.1155/2016/4709572. CrossRef

Yu T, Volponi AA, Babb R, An Z, Sharpe PT. Stem Cells in Tooth Development, Growth, Repair, and Regeneration. Curr Top Dev Biol. 2015; 115: 187-212. CrossRef

Arthur A, Shi S, Gronthos S. Dental Pulp Stem Cells. In: Vishwakarma A, Sharpe P, Shi Songtau, Ramalingam M, editors. Stem Cell Biology and Tissue Engineering in Dental Sciences. Oxford: Elsevier Inc; 2015. p.279-89. Link

Sharpe PT. Dental msenchymal stem cells. Development. 2016; 143: 2273-80. CrossRef

Cho SW, Hwang HJ, Kim JY, Song WC, Song SJ, Yamamoto H, et al. Lineage of non-cranial neural crest cell in the dental mesenchyme: using a lacZ reporter gene during early tooth development. J Electron Microsc (Tokyo). 2003; 52(6): 567-71. CrossRef

Zhang Y, Wang S, Song Y, Han J, Chai Y, Chen Y. Timing of odontogenic neural crest cell migration and tooth-forming capability in mice. Dev Dyn. 2003; 226(4): 713-8. CrossRef

Li J, Huang X, Xu X, Mayo J, Bringas P, Jiang R et al. SMAD4-mediated WNT signaling controls the fate of cranial neural crest cells during tooth morphogenesis. Development. 2011; 138(10): 1977-89. CrossRef

Chai Y, Jiang X, Ito Y, Bringas PJr, Han J, Rowitch DH, et al. Fate of the mammalian cranial neural crest during tooth and mandibular morphogenesis. Development. 2000; 127(8): 1671-9. Link

Rodríguez-Lozano FJ, Insausti CL, Iniesta F, Blanquer M, Ramírez MD, Meseguer L, et al. Mesenchymal dental stem cells in regenerative dentistry. Med Oral Patol Oral Cir Bucal. 2012; 17(6): e1062-7. CrossRef

Huang GT, 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(9): 792-806. CrossRef

Shilpa PS, Kaul R, Sultana N, Bhat S. Stem cells: Boon to dentistry and medicine. Dent Res J (Isfahan). 2013; 10(2): 149-54. Link

Gronthos S, Mankani M, Brahim J, Robey PG, Shi S. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci USA. 2000; 97(25): 13625-30. CrossRef

Alge DL, Zhou D, Adams LL, Wyss BK, Shadday MD, Woods EJ, et al. Donor-matched comparison of dental pulp stem cells and bone marrow-derived mesenchymal stem cells in a rat model. J Tissue Eng Regen Med. 2010; 4(1): 73-81. CrossRef

Murray PE, Garcia-Godoy F, Hargreaves KM. Regenerative endodontics: A review of current status and a call for action. J Endod. 2007; 33(4): 377-90. CrossRef

Kerkis I, Kerkis A, Dozortsev D, Stukart-Parsons GC, Gomes Massironi SM, Pereira LV, et al. Isolation and characterization of a population of immature dental pulp stem cells expressing OCT-4 and other embryonic stem cell markers. Cells Tissues Organs. 2006; 184(3-4): 105-16. CrossRef

Bakopoulou A, About I. Stem Cells of Dental Origin : Current Research Trends and Key Milestones towards Clinical Application. Stem Cell Int. 2016; 2016: 4209891. doi: 10.1155/2016/4209891. CrossRef

Potdar PD, Jethmalani YD. Human dental pulp stem cells: Applications in future regenerative medicine. World J Stem Cells. 2015; 7(5): 839-51. CrossRef

Gomes JA, Geraldes Monterio B, Melo GB, Smith RL, Cavenaghi Pereira da Silva M, Lizier NF, et al. Corneal reconstruction with tissue-engineered cell sheets composed of human immature dental pulp stem cells. Invest Ophthalmol Vis Sci. 2010; 51(3): 1408-14. CrossRef

Tran HLB, Dinh TTH, Nguyen HTT. Stem cells from apical papilla and their properties in two primary culture methods. International Journal of Biomedical Research. 2014; 5(8): 516-21. CrossRef

Ruparel NB, de Almeida JF, Henry MA, Diogenes A. Characterization of a stem cell of apical papilla cell line: effect of passage on cellular phenotype. J Endod. 2013; 39(3): 357-63. CrossRef

Sonoyama W, Liu Y, Yamaza T, Tuan RS, Wang S, Shi S, et al. Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: a pilot study. J Endod. 2008; 34(2): 166-71. CrossRef

Morsczeck C. Dental Follicle Stem Cells. In: Vishwakarma A, Sharpe P, Shi Songtau, Ramalingam M, editors. Stem Cell Biology and Tissue Engineering in Dental Sciences. Oxford: Elsevier Inc; 2015. p.271-77. Link

Miura M, Gronthos S, Zhao M, Lu B, Fisher LW, Robey PG, et al. SHED: Stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci U S A. 2003; 100(10): 5807-12. CrossRef

Suchánek J, Visek B, Soukup T, El-Din Mohamed SK, Ivančaková R, Mokrý J et al. Stem cells from human exfoliated deciduous teeth--isolation, long term cultivation and phenotypical analysis. Acta Medica (Hradec Kralove). 2010; 53(2): 93-9. Link

Martinez Saez D, Sasaki RT, Neves AD, da Silva MC. Stem Cells from Human Exfoliated Deciduous Teeth: A Growing Literature. Cells Tissues Organs. 2016; 202(5-6): 269-80. CrossRef

Wang X, Sha XJ, Li GH, Yang FS, Ji K, Wen LY, et al. Comparative characterization of stem cells from human exfoliated deciduous teeth and dental pulp stem cells. Arch Oral Biol. 2012; 57(9): 1231-40. CrossRef

Saito MT, Silvério KG, Casati MZ, Sallum EA, Nociti FH Jr. Tooth-derived stem cells: Update and perspectives. World J of Stem Cells. 2015; 7(2): 399-407. CrossRef

Nourbakhsh N, Soleimani M, Taghipour Z, Karbalaie K, Mousavi SB, Talebi A, et al. Induced in vitro differentiation of neural-like cells from human exfoliated deciduous teeth-derived stem cells. Int J Dev Biol. 2011; 55(2): 189-95. CrossRef

Bansal R, Jain A. Current overview on dental stem cells applications in regenerative dentistry. J Nat Sci Biol Med. 2015; 6(1): 29-34. CrossRef

Seo BM, Miura M, Gronthos S, Bartold PM, Batouli S, Brahim J, et al. Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet. 2004; 364(9429): 149-55. CrossRef

Barczyk M, Bolstad AI, Gullberg D. Role of integrins in the periodontal ligament: organizers and facilitators. Periodontol 2000. 2013; 63(1): 29-47. CrossRef

Diomede F, Zini N, Gatta V, Fulle S, Merciaro I, D’Aurora M, et al. Human periodontal ligament stem cells cultured onto cortico-cancellous scaffold drive bone regenerative process. Eur Cell Mater. 2016; 32: 181-201. CrossRef

Seo BM, Miura M, Sonoyama W, Coppe C, Staynon R, Shi S. Recovery of stem cells from cryopreserved periodontal ligament. J Dent Res. 2005; 84(10): 907-12. CrossRef

Gay IC, Chen S, MacDougall M. Isolation and characterization of multipotent human periodontal ligament stem cells. Orthod Craniofac Res. 2007; 10(3): 149-60. CrossRef

Zhu W, Liang M. Periodontal ligament stem cells: current status, concerns, and future prospects. Stem Cells Int. 2015; 2015: 972313. doi: 10.1155/2015/972313. CrossRef

Lucaciu O, Soriţău O, Gheban D, Ciuca DR, Virtic O, Vulpoi A, et al. Dental follicle stem cells in bone regeneration on titanium implants. BMC Biotechnol. 2015; 15: 114. doi: 10.1186/s12896-015-0229-6. CrossRef

Rezai-Rad M, Bova JF, Orooji M, Pepping J, Qureshi A, Del Piero F, et al. Evaluation of bone regeneration potential of dental follicle stem cells for treatment of craniofacial defects. Cytotherapy. 2015; 17(11): 1572-81. CrossRef

Priya SP, Higuchi A, Fanas SA, Ling MP, Neela VK, Sunil PM, et al. Odontogenic epithelial stem cells: hidden sources. Lab Invest. 2015; 95(12): 1344-52. CrossRef

Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001; 7(2): 211-28. CrossRef

Matsubara T, Suardita K, Ishii M, Sugiyama M, Igarashi A, Oda R, et al. Alveolar bone marrow as a cell source for regenerative medicine: differences between alveolar and iliac bone marrow stromal cells. J Bone Miner Res. 2005; 20(3): 399-409. CrossRef

Akintoye SO, Lam T, Shi S, Brahim J, Collins MT, Robey PG. Skeletal site-specific characterization of orofacial and iliac crest human bone marrow stromal cells in same individuals. Bone. 2006; 38(6): 758-68. CrossRef

Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS, et al. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell. 2008; 3(3): 301-13. CrossRef

Mailhot JM, Borke JL. An Isolation and In Vitro Culturing Method for Human Intraoral Bone Cells Derived from Dental Implant Preparation Sites. Clin Oral Implants Res. 1998; 9(1): 43-50. CrossRef

Cicconetti A, Sacchetti B, Bartoli A, Michienzi S, Corsi A, Funari 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(5): 618.e1-12. CrossRef

Jo YY, Lee HJ, Kook SY, Choung HW, Park JY, Chung JH, et al. Isolation and Characterization of Postnatal Stem Cells from Human Dental Tissues. Tissue Eng. 2007; 13(4): 767-73. CrossRef

Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal Criteria for Defining Multipotent Mesenchymal Stromal Cells. The International Society for Cellular Therapy Position Statement. Cytotherapy. 2006; 8(4): 315-7. CrossRef

Lubis AM, Sandhow L, Lubis VK, Noor A, Gumay F, Merlina M, et al. Isolation and Cultivation of Mesenchymal Stem Cells from Iliac Crest Bone Marrow for Further Cartilage Defect Management. Acta Med Indones. 2011; 43(3): 178-84. Link

Mao X, Liu Y, Chen C, Shi S. Mesenchymal Stem Cells And Their Role In Dental Medicine. Dent Clin North Am. 2017; 61(1): 161-72. CrossRef

Ryan JM, Barry FP, Murphy JM, Mahon BP. Mesenchymal Stem Cells Avoid Allogeneic Rejection. J Inflamm (Lond). 2005; 2: 8. doi: 10.1186/1476-9255-2-8. CrossRef

Widowati W, Sardjono CT, Wijaya L, Laksmitawati DR, Sandra F. Extract of Curcuma longa L. and (-)-Epigallocatechin-3-Gallate Enhanced Proliferation of Adipose Tissue-derived Mesenchymal Stem Cells (AD-MSCs) and Differentiation of AD-MSCs into Endothelial Progenitor Cells. Journal of US-China Med Sci. 2012; 9(1): 22-9. Link

Sardjono CT, Setiawan M, Frisca, Saputra V, Aniko G, Sandra F. Application of a modified method for stem cell isolation from lipoaspirates in a basic lab. Med J Indones. 2009; 18(2): 91-6. CrossRef

Bara J, Richards R, Alini M, Stoddart M. Concise review: Bone marrow-Derived Mesenchymal Stem Cells Change Phenotype Following In Vitro Culture: Implications for Basic Research and The Clinic. Stem Cells. 2014; 32(7): 1713-23. CrossRef

Djuwantono T, Wirakusumah FF, Achmad TH, Sandra F, Halim D, Faried A. A comparison of cryopreservation methods: Slow-cooling vs. rapid-cooling based on cell viability, oxidative stress, apoptosis, and CD34+ enumeration of human umbilical cord blood mononucleated cells. BMC Res Notes. 2011; 4: 371. doi: 10.1186/1756-0500-4-371. CrossRef

Wijaya L, Agustina D, Lizandi AO, Kartawinata MM, Sandra F. Reversing Breast Cancer Stem Cell into Breast Somatic Stem Cell. Curr Pharm Biotechnol. 2011; 12(2): 189-95. CrossRef

Mark P, Kleinsorge M, Gaebel R, Lux CA, Toelk A, Pittermann E, et al. Human Mesenchymal Stem Cells Display Reduced Expression of CD105 after Culture in Serum-Free Medium. Stem Cells Int. 2013; 2013: 698076. doi: 10.1155/2013/698076. CrossRef

Maleki M, Ghanbarvand F, Behvarz MR, Ejtemaei M, Ghadirkhomi E. Comparison of Mesenchymal Stem Cell Markers in Multiple Human Adult Stem Cells. Int J Stem Cells. 2014; 7(2): 118-26. CrossRef

Barry FP, Boynton RE, Haynesworth S, Murphy JM, Zaia J. The monoclonal antibody SH-2, raised against human mesenchymal stem cells, recognizes an epitope on endoglin (CD105). Biochem Biophys Res Commun. 1999; 265(1): 134-9. CrossRef

Roura S, Farré J, Soler-Botija C, Llach A, Hove-Madsen L, Cairó JJ, et al. Effect of aging on the pluripotential capacity of human CD105+ mesenchymal stem cells. Eur J Heart Fail. 2006; 8(6): 555-63. CrossRef

Rege TA, Hagood JS. Thy-1 as a regulator of cell-cell and cell-matrix interactions in axon regeneration, apoptosis, adhesion, migration, cancer, and fibrosis. FASEB J. 2006; 20(8): 1045-54. CrossRef

Ledda M, Fosca M, Bonis AD, Curcio M, Teghil R, Lolli MG, et al. Placenta Derived Mesenchymal Stem Cells Hosted on RKKP Glass-Ceramic: A Tissue Engineering Strategy for Bone Regenerative Medicine Applications. Biomed Res Int. 2016; 2016: 3657906. doi: 10.1155/2016/3657906. CrossRef

Sobhani A , Khanlarkhand N, Baazm M, Mohammadzadeh F, Najafi A, Mehdinejadiani S, et al. Multipotent Stem Cell and Current Application. Acta Med Iran. 2017; 55(1): 6-23. Link

Halim D, Murti H, Sandra F, Boediono A, Djuwantono T, Setiawan B. Stem Cell: Dasar Teori & Aplikasi Klinis. Jakarta: Erlangga; 2010. Link

Ren H, Sang Y, Zhang F, Liu Z, Qi N, Chen Y. Comparative Analysis of Human Mesenchymal Stem Cells from Umbilical Cord, Dental Pulp, and Menstrual Blood as Sources for Cell Therapy. Stem Cells Int. 2016; 2016: 3516574. doi: 10.1155/2016/3516574. CrossRef

Balaji S, Keswani SG, Crombleholme TM. The Role of Mesenchymal Stem Cells in The Regenerative Wound Healing Phenotype. Adv Wound Care (New Rochelle). 2012; 1(4): 159-65. CrossRef

Kim N, Cho SG. Clinical Applications of Mesenchymal Stem Cells. Korean J Intern Med. 2013; 28(4): 387-402. CrossRef


Copyright (c) 2017 Molecular and Cellular Biomedical Sciences

Indexed by:





Cell and BioPharmaceutical Institute