Human dental pulp stem cells demonstrate better neural and epithelial stem cell properties than bone marrow-derived mesenchymal stem cells

  • Erdal Karaöz
  • Pınar Cetinalp Demircan
  • Özlem Sağlam
  • Ayca Aksoy
  • Figen Kaymaz
  • Gökhan Duruksu
Original Paper


Dental pulp stem cells (hDP-SCs) were primarily derived from pulp tissues of primary incisors, exfoliated deciduous and permanent third molar teeth. To understand the characteristics of hDP-SCs from impacted third molar, proliferation capacities, gene expression profiles, phenotypic, ultrastructural, and differentiation characteristics were analyzed in comparison with human bone marrow-derived mesenchymal stem cells (hBM-MSCs), extensively. hDP-SCs showed more developed and metabolically active cells. Contrary to hBM-MSCs, hDP-SCs strongly expressed both cytokeratin (CK)-18 and -19, which could involve in odontoblast differentiation and dentine repair. The intrinsic neuro-glia characteristics of hDP-MSCs were demonstrated by the expression of several specific transcripts and proteins of neural stem cell and neurons. These cells not only differentiate into adipogenic, osteogenic, and chondrogenic lineage, but also share some special characteristics of expressing some neural stem cell and epithelial markers. Under defined conditions, hDP-SCs are able to differentiate into both neural and vascular endothelial cells in vitro. Dental pulp might provide an alternative source for human MSCs. hDP-SCs with a promising differentiation capacity could be easily isolated, and possible clinical use could be developed for neurodegenerative and oral diseases in the future.


Dental pulp Third molar Bone marrow Mesenchymal stem cells Cell differentiation 



This study was supported by grants [108S404] and [108S291] of the Scientific and Research Council of Turkey (TUBITAK). We thank Alpaslan Okcu and Cansu Subası for their excellent technical assistance.

Conflict of interest

The authors have declared that no conflict of interest exists.

Supplementary material

418_2011_858_MOESM1_ESM.pdf (444 kb)
Supplementary material 1 (PDF 443 kb)
418_2011_858_MOESM2_ESM.pdf (318 kb)
Supplementary material 2 (PDF 317 kb)
418_2011_858_MOESM3_ESM.pdf (675 kb)
Supplementary material 3 (PDF 674 kb)
418_2011_858_MOESM4_ESM.pdf (80 kb)
Supplementary material 4 (PDF 80 kb)
418_2011_858_MOESM5_ESM.pdf (689 kb)
Supplementary material 5 (PDF 689 kb)
418_2011_858_MOESM6_ESM.pdf (1 mb)
Supplementary material 6 (PDF 1041 kb)
418_2011_858_MOESM7_ESM.pdf (174 kb)
Supplementary material 7 (PDF 173 kb)
418_2011_858_MOESM8_ESM.pdf (224 kb)
Supplementary material 8 (PDF 224 kb)
418_2011_858_MOESM9_ESM.pdf (190 kb)
Supplementary material 9 (PDF 189 kb)
418_2011_858_MOESM10_ESM.pdf (485 kb)
Supplementary material 10 (PDF 484 kb)
418_2011_858_MOESM11_ESM.pdf (455 kb)
Supplementary material 11 (PDF 454 kb)


  1. Aksu AE, Horibe E, Sacks J, Ikeguchi R, Breitinger J, Scozio M, Unadkat J, Feili-Hariri M (2008) Co-infusion of donor bone marrow with host mesenchymal stem cells treats GVHD and promotes vascularized skin allograft survival in rats. Clin Immunol 127:348–358PubMedCrossRefGoogle Scholar
  2. Ball LM, Bernardo ME, Roelofs H, Lankester A, Cometa A, Egeler RM, Locatelli F, Fibbe WE (2007) Cotransplantation of ex vivo expanded mesenchymal stem cells accelerates lymphocyte recovery and may reduce the risk of graft failure in haploidentical hematopoietic stem-cell transplantation. Blood 110:2764–2767PubMedCrossRefGoogle Scholar
  3. Bhatia B, Singhal S, Tadman DN, Khaw PT, Limb GA (2010) SOX2 is required for adult human Muller stem cell survival and maintenance of progenicity in vitro. Invest Ophthalmol Vis Sci 52:136–145CrossRefGoogle Scholar
  4. Boumaza I, Srinivasan S, Witt WT, Feghali-Bostwick C, Dai Y, Garcia-Ocana A, Feili-Hariri M (2009) Autologous bone marrow-derived rat mesenchymal stem cells promote PDX-1 and insulin expression in the islets, alter T cell cytokine pattern and preserve regulatory T cells in the periphery and induce sustained normoglycemia. J Autoimmun 32:33–42PubMedCrossRefGoogle Scholar
  5. Bryan TM, Englezou A, Gupta J, Bacchetti S, Reddel RR (1995) Telomere elongation in immortal human cells without detectable telomerase activity. EMBO J 14:4240–4248PubMedGoogle Scholar
  6. Chan JL, Tang KC, Patel AP, Bonilla LM, Pierobon N, Ponzio NM, Rameshwar P (2006) Antigen-presenting property of mesenchymal stem cells occurs during a narrow window at low levels of interferon-gamma. Blood 107:4817–4824PubMedCrossRefGoogle Scholar
  7. Comoli P, Ginevri F, Maccario R, Avanzini MA, Marconi M, Groff A, Cometa A, Cioni M, Porretti L, Barberi W, Frassoni F, Locatelli F (2008) Human mesenchymal stem cells inhibit antibody production induced in vitro by allostimulation. Nephrol Dial Transplant 23:1196–1202PubMedCrossRefGoogle Scholar
  8. d’Aquino R, Graziano A, Sampaolesi M, Laino G, Pirozzi G, De Rosa A, Papaccio G (2007) Human postnatal dental pulp cells co-differentiate into osteoblasts and endotheliocytes: a pivotal synergy leading to adult bone tissue formation. Cell Death Differ 14:1162–1171PubMedCrossRefGoogle Scholar
  9. Domingues MG, Jaeger MM, Araujo VC, Araujo NS (2000) Expression of cytokeratins in human enamel organ. Eur J Oral Sci 108:43–47PubMedCrossRefGoogle Scholar
  10. Fu XY (2006) STAT3 in immune responses and inflammatory bowel diseases. Cell Res 16:214–219PubMedCrossRefGoogle Scholar
  11. Gandia C, Arminan A, Garcia-Verdugo JM, Lledo E, Ruiz A, Minana MD, Sanchez-Torrijos J, Paya R, Mirabet V, Carbonell-Uberos F, Llop M, Montero JA, Sepulveda P (2008) Human dental pulp stem cells improve left ventricular function, induce angiogenesis, and reduce infarct size in rats with acute myocardial infarction. Stem Cells 26:638–645PubMedCrossRefGoogle Scholar
  12. Gronthos S, Mankani M, Brahim J, Robey PG, Shi S (2000) Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci USA 97:13625–13630PubMedCrossRefGoogle Scholar
  13. Gronthos S, Brahim J, Li W, Fisher LW, Cherman N, Boyde A, DenBesten P, Robey PG, Shi S (2002) Stem cell properties of human dental pulp stem cells. J Dent Res 81:531–535PubMedCrossRefGoogle Scholar
  14. Huang AH, Chen YK, Lin LM, Shieh TY, Chan AW (2008) Isolation and characterization of dental pulp stem cells from a supernumerary tooth. J Oral Pathol Med 37:571–574PubMedCrossRefGoogle Scholar
  15. Iohara K, Nakashima M, Ito M, Ishikawa M, Nakasima A, Akamine A (2004) Dentin regeneration by dental pulp stem cell therapy with recombinant human bone morphogenetic protein 2. J Dent Res 83:590–595PubMedCrossRefGoogle Scholar
  16. Jo YY, Lee HJ, Kook SY, Choung HW, Park JY, Chung JH, Choung YH, Kim ES, Yang HC, Choung PH (2007) Isolation and characterization of postnatal stem cells from human dental tissues. Tissue Eng 13:767–773PubMedCrossRefGoogle Scholar
  17. Karaoz E, Okcu A, Gacar G, Saglam O, Yuruker S, Kenar H (2010) A Comprehensive characterization study of human bone marrow MSCs with an emphasis on molecular and ultrastructural properties. J Cell Physiol 226:1367–1382CrossRefGoogle Scholar
  18. Kashatus D, Cogswell P, Baldwin AS (2006) Expression of the Bcl-3 proto-oncogene suppresses p53 activation. Genes Dev 20:225–235PubMedCrossRefGoogle Scholar
  19. Laino G, d’Aquino R, Graziano A, Lanza V, Carinci F, Naro F, Pirozzi G, Papaccio G (2005) A new population of human adult dental pulp stem cells: a useful source of living autologous fibrous bone tissue (LAB). J Bone Miner Res 20:1394–1402PubMedCrossRefGoogle Scholar
  20. Le Blanc K, Rasmusson I, Sundberg B, Götherström C, Hassan M, Uzunel M, Ringden O (2004) Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 363:1439–1441PubMedCrossRefGoogle Scholar
  21. Lee ST, Jang JH, Cheong JW, Kim JS, Maemg HY, Hahn JS, Ko YW, Min YH (2002) Treatment of high-risk acute myelogenous leukaemia by myeloablative chemoradiotherapy followed by co-infusion of T cell-depleted haematopoietic stem cells and culture-expanded marrow mesenchymal stem cells from a related donor with one fully mismatched human leucocyte antigen haplotype. Br J Haematol 118:1128–1131PubMedCrossRefGoogle Scholar
  22. Lim JH, Boozer L, Mariani CL, Piedrahita JA, Olby NJ (2010) Generation and characterization of neurospheres from canine adipose tissue-derived stromal cells. Cell Reprogram 12:417–425PubMedGoogle Scholar
  23. Lindroos B, Maenpaa K, Ylikomi T, Oja H, Suuronen R, Miettinen S (2008) Characterisation of human dental stem cells and buccal mucosa fibroblasts. Biochem Biophys Res Commun 368:329–335PubMedCrossRefGoogle Scholar
  24. McKay R (1997) Stem cells in the central nervous system. Science 5309:66–71CrossRefGoogle Scholar
  25. Morandi F, Raffaghello L, Bianchi G, Meloni F, Salis A, Millo E, Ferrone S, Barnaba V, Pistoia V (2008) Immunogenicity of human mesenchymal stem cells in HLA-class I-restricted T cell responses against viral or tumor-associated antigens. Stem Cells 26:1275–1287PubMedCrossRefGoogle Scholar
  26. Myginda T, Stiehler M, Baatrup A, Li H, Zou X, Flyvbjerg A, Kassem M, Bünger C (2007) Mesenchymal stem cell ingrowth and differentiation on coralline hydroxyapatite scaffolds. Biomaterials 28:1036–1047CrossRefGoogle Scholar
  27. Nauta AJ, Kruisselbrink AB, Lurvink E, Willemze R, Fibbe WE (2006) Mesenchymal stem cells inhibit generation and function of both CD34 + derived and monocyte derived dendritic cells. J Immunol 177:2080–2087PubMedGoogle Scholar
  28. Niu G, Wright KL, Huang M, Song L, Haura E, Turkson J, Zhang S, Wang T, Sinibaldi D, Coppola D, Heller R, Ellis LM, Karras J, Bromberg J, Pardoll D, Jove R, Yu H (2002) Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis. Oncogene 21:2000–2008PubMedCrossRefGoogle Scholar
  29. Nosrat IV, Widenfalk J, Olson L, Nosrat CA (2001) Dental pulp cells produce neurotrophic factors, interact with trigeminal neurons in vitro, and rescue motoneurons after spinal cord injury. Dev Biol 238:120–132PubMedCrossRefGoogle Scholar
  30. Ono K, Han J (2000) The p38 signal transduction pathway: activation and function. Cell Signal 12:1–13PubMedCrossRefGoogle Scholar
  31. Opipari AW Jr, Boguski MS, Dixit VM (1990) The A20 cDNA induced by tumor necrosis factor alpha encodes a novel type of zinc finger protein. J Biol Chem 265:14705–14708PubMedGoogle Scholar
  32. Otaki S, Ueshima S, Shiraishi K, Sugiyama K, Hamada S, Yorimoto M, Matsuo O (2007) Mesenchymal progenitor cells in adult human dental pulp and their ability to form bone when transplanted into immunocompromised mice. Cell Biol Int 31:1191–1197PubMedCrossRefGoogle Scholar
  33. Phinney DG, Prockop DJ (2007) Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair-current views. Stem Cells 25:2896–2902PubMedCrossRefGoogle Scholar
  34. Russo RE, Reali C, Radmilovich M, Fernandez A, Trujillo-Cenóz O (2008) Connexin 43 delimits functional domains of neurogenic precursors in the spinal cord. J Neurosci 28:3298–3309PubMedCrossRefGoogle Scholar
  35. Spaggiari GM, Capobianco A, Abdelrazik H, Becchetti F, Mingari MC, Moretta L (2008) Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2, 3-dioxygenase and prostaglandin E2. Blood 111:1327–1333PubMedCrossRefGoogle Scholar
  36. Stagg J, Pommey S, Eliopoulos N, Galipeau J (2006) Interferon-gamma-stimulated marrow stromal cells: a new type of nonhematopoietic antigen-presenting cell. Blood 107:2570–2577PubMedCrossRefGoogle Scholar
  37. Tai M, Chang C, Olson LK, Trosko JE (2005) Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis 26:495–502PubMedCrossRefGoogle Scholar
  38. Tang YL, Zhao Q, Zhang YC, Cheng L, Liu M, Shi J, Yang YZ, Pan C, Ge J, Phillips MI (2004) Autologous mesenchymal stem cell transplantation induce VEGF and neovascularization in ischemic myocardium. Regul Pept 117:3–10PubMedCrossRefGoogle Scholar
  39. Tse WT, Pendleton JD, Beyer WM, Egalka MC, Guinan EC (2003) Suppression of allogeneic T cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation 75:389–397PubMedCrossRefGoogle Scholar
  40. Uemura R, Xu M, Ahmad N, Ashraf M (2006) Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling. Circ Res 98:1414–1421PubMedCrossRefGoogle Scholar
  41. von Holst A, Egbers U, Prochiantz A, Faissner A (2007) Neural stem/progenitor cells express 20 tenascin C isoforms that are differentially regulated by Pax6. J Biol Chem 282:9172–9181CrossRefGoogle Scholar
  42. Wang M, Crisostomo PR, Herring C, Meldrum KK, Meldrum DR (2006) Human progenitor cells from bone marrow or adipose tissue produce VEGF, HGF, and IGF-I in response to TNF by a p38 MAPKdependent mechanism. Am J Physiol Regul Integr Comp Physiol 291:R880–R884PubMedCrossRefGoogle Scholar
  43. Wang M, Zhang W, Crisostomo P, Markel T, Meldrum KK, Fu XY, Meldrum DR (2007) STAT3 mediates bone marrow mesenchymal stem cell VEGF production. J Mol Cell Cardiol 42:1009–1015PubMedCrossRefGoogle Scholar
  44. Wei D, Le X, Zheng L, Wang L, Frey JA, Gao AC, Peng Z, Huang S, Xiong HQ, Abbruzzese JL, Xie K (2003) Stat3 activation regulates the expression of vascular endothelial growth factor and human pancreatic cancer angiogenesis and metastasis. Oncogene 22:319–329PubMedCrossRefGoogle Scholar
  45. Yalvac ME, Ramazanoglu M, Tekguc M, Bayrak OF, Shafigullina AK, Salafutdinov II, Blatt NL, Kiyasov AP, Sahin F, Palotás A, Rizvanov AA (2010) Human tooth germ stem cells preserve neuro-protective effects after long-term cryo-preservation. Curr Neurovasc Res 7:49–58PubMedCrossRefGoogle Scholar
  46. Yu J, Wang Y, Deng Z, Tang L, Li Y, Shi J, Jin Y (2007) Odontogenic capability: bone marrow stromal stem cells versus dental pulp stem cells. Biol Cell 99:465–474PubMedCrossRefGoogle Scholar
  47. Zhao DC, Lei JX, Chen R, Yu WH, Zhang XM, Li SN, Xiang P (2005) Bone marrow-derived mesenchymal stem cells protect against experimental liver fibrosis in rats. World J Gastroenterol 11:3431–3440PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Erdal Karaöz
    • 1
  • Pınar Cetinalp Demircan
    • 1
  • Özlem Sağlam
    • 1
  • Ayca Aksoy
    • 1
  • Figen Kaymaz
    • 2
  • Gökhan Duruksu
    • 1
  1. 1.Department of Stem Cell, Center for Stem Cell and Gene Therapies Research and Practice, Institute of Health SciencesKocaeli UniversityKocaeliTurkey
  2. 2.Faculty of Medicine, Department of Histology and EmbryologyHacettepe UniversityAnkaraTurkey

Personalised recommendations