Clinical Oral Investigations

, Volume 17, Issue 9, pp 1969–1983 | Cite as

Dental stem cells and their promising role in neural regeneration: an update

  • W. Martens
  • A. Bronckaers
  • C. Politis
  • R. Jacobs
  • I. Lambrichts



Stem cell-based therapies are considered to be a promising treatment method for several clinical conditions such as Alzheimer's disease, Parkinson's disease, spinal cord injury, and many others. However, the ideal stem cell type for stem cell-based therapy remains to be elucidated.


Stem cells are present in a variety of tissues in the embryonic and adult human body. Both embryonic and adult stem cells have their advantages and disadvantages concerning the isolation method, ethical issues, or differentiation potential. The most described adult stem cell population is the mesenchymal stem cells due to their multi-lineage (trans)differentiation potential, high proliferative capacity, and promising therapeutic values. Recently, five different cell populations with mesenchymal stem cell characteristics were identified in dental tissues: dental pulp stem cells, stem cells from human exfoliated deciduous teeth, periodontal ligament stem cells, dental follicle precursor cells, and stem cells from apical papilla.


Each dental stem cell population possesses specific characteristics and advantages which will be summarized in this review. Furthermore, the neural characteristics of dental pulp stem cells and their potential role in (peripheral) neural regeneration will be discussed.


Dental stem cells Neural characteristics Tooth development Stem cells 



W. Martens and A. Bronckaers are supported by grants from the ‘Fonds voor Wetenschappelijk Onderzoek’, Belgium.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Ibarretxe G, Crende O, Aurrekoetxea M, Garcia-Murga V, Etxaniz J, Unda F (2012) Neural crest stem cells from dental tissues: a new hope for dental and neural regeneration. Stem Cells Int. doi: 10.1155/2012/103503, 103503Google Scholar
  2. 2.
    Rimondini L, Mele S (2009) Stem cell technologies for tissue regeneration in dentistry. Minerva Stomatol 58(10):483–500PubMedGoogle Scholar
  3. 3.
    Park HW, Lim MJ, Jung H, Lee SP, Paik KS, Chang MS (2010) Human mesenchymal stem cell-derived Schwann cell-like cells exhibit neurotrophic effects, via distinct growth factor production, in a model of spinal cord injury. Glia 58(9):1118–1132. doi: 10.1002/glia.20992 PubMedGoogle Scholar
  4. 4.
    Sakai K, Yamamoto A, Matsubara K, Nakamura S, Naruse M, Yamagata M, Sakamoto K, Tauchi R, Wakao N, Imagama S, Hibi H, Kadomatsu K, Ishiguro N, Ueda M (2012) Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms. J Clin Investig 122(1):80–90. doi: 10.1172/JCI59251 PubMedGoogle Scholar
  5. 5.
    Ross JJ, Verfaillie CM (2008) Evaluation of neural plasticity in adult stem cells. Philos Trans R Soc Lond 363(1489):199–205Google Scholar
  6. 6.
    Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284(5411):143–147PubMedGoogle Scholar
  7. 7.
    Meirelles Lda S, Fontes AM, Covas DT, Caplan AI (2009) Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine Growth Factor Rev 20(5–6):419–427PubMedGoogle Scholar
  8. 8.
    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 U S A 97(25):13625–13630PubMedGoogle Scholar
  9. 9.
    Miura M, Gronthos S, Zhao M, Lu B, Fisher LW, Robey PG, Shi S (2003) SHED: stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci U S A 100(10):5807–5812PubMedGoogle Scholar
  10. 10.
    Morsczeck C, Gotz W, Schierholz J, Zeilhofer F, Kuhn U, Mohl C, Sippel C, Hoffmann KH (2005) Isolation of precursor cells (PCs) from human dental follicle of wisdom teeth. Matrix Biol 24(2):155–165PubMedGoogle Scholar
  11. 11.
    Seo BM, Miura M, Gronthos S, Bartold PM, Batouli S, Brahim J, Young M, Robey PG, Wang CY, Shi S (2004) Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 364(9429):149–155PubMedGoogle Scholar
  12. 12.
    Sonoyama W, Liu Y, Yamaza T, Tuan RS, Wang S, Shi S, Huang GT (2008) Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: a pilot study. J Endod 34(2):166–171. doi: 10.1016/j.joen.2007.11.021 PubMedGoogle Scholar
  13. 13.
    Lakshmipathy U, Verfaillie C (2005) Stem cell plasticity. Blood Rev 19(1):29–38PubMedGoogle Scholar
  14. 14.
    Verfaillie CM, Pera MF, Lansdorp PM (2002) Stem cells: hype and reality. Hematology 1:369–391Google Scholar
  15. 15.
    Friedenstein AJ, Gorskaja JF, Kulagina NN (1976) Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp Hematol 4(5):267–274PubMedGoogle Scholar
  16. 16.
    Bianco P, Riminucci M, Gronthos S, Robey PG (2001) Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells 19(3):180–192PubMedGoogle Scholar
  17. 17.
    Bruder SP, Jaiswal N, Haynesworth SE (1997) Growth kinetics, self-renewal, and the osteogenic potential of purified human mesenchymal stem cells during extensive subcultivation and following cryopreservation. J Cell Biochem 64(2):278–294PubMedGoogle Scholar
  18. 18.
    Guillot PV, Cui W, Fisk NM, Polak DJ (2007) Stem cell differentiation and expansion for clinical applications of tissue engineering. J Cell Mol Med 11(5):935–944PubMedGoogle Scholar
  19. 19.
    Spencer ND, Gimble JM, Lopez MJ (2011) Mesenchymal stromal cells: past, present, and future. Vet Surg 40(2):129–139PubMedGoogle Scholar
  20. 20.
    Kopen GC, Prockop DJ, Phinney DG (1999) Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci U S A 96(19):10711–10716PubMedGoogle Scholar
  21. 21.
    Lu D, Li Y, Wang L, Chen J, Mahmood A, Chopp M (2001) Intraarterial administration of marrow stromal cells in a rat model of traumatic brain injury. J Neurotrauma 18(8):813–819PubMedGoogle Scholar
  22. 22.
    Chen J, Li Y, Wang L, Lu M, Zhang X, Chopp M (2001) Therapeutic benefit of intracerebral transplantation of bone marrow stromal cells after cerebral ischemia in rats. J Neurol Sci 189(1–2):49–57PubMedGoogle Scholar
  23. 23.
    Hofstetter CP, Schwarz EJ, Hess D, Widenfalk J, El Manira A, Prockop DJ, Olson L (2002) Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery. Proc Natl Acad Sci U S A 99(4):2199–2204PubMedGoogle Scholar
  24. 24.
    Chen SL, Fang WW, Qian J, Ye F, Liu YH, Shan SJ, Zhang JJ, Lin S, Liao LM, Zhao RC (2004) Improvement of cardiac function after transplantation of autologous bone marrow mesenchymal stem cells in patients with acute myocardial infarction. Chin Med J 117(10):1443–1448PubMedGoogle Scholar
  25. 25.
    Horwitz EM, Gordon PL, Koo WK, Marx JC, Neel MD, McNall RY, Muul L, Hofmann T (2002) Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: implications for cell therapy of bone. Proc Natl Acad Sci U S A 99(13):8932–8937PubMedGoogle Scholar
  26. 26.
    Horwitz EM, Prockop DJ, Gordon PL, Koo WW, Fitzpatrick LA, Neel MD, McCarville ME, Orchard PJ, Pyeritz RE, Brenner MK (2001) Clinical responses to bone marrow transplantation in children with severe osteogenesis imperfecta. Blood 97(5):1227–1231PubMedGoogle Scholar
  27. 27.
    Nanci A (2008) Ten Cate's oral histology: development, structure, and function, 6th edn. Mosby Elsevier, PhiladelphiaGoogle Scholar
  28. 28.
    Thesleff I, Jernvall J (1997) The enamel knot: a putative signaling center regulating tooth development. Cold Spring Harb Symp Quant Biol 62:257–267PubMedGoogle Scholar
  29. 29.
    Sonoyama W, Liu Y, Fang D, Yamaza T, Seo BM, Zhang C, Liu H, Gronthos S, Wang CY, Wang S, Shi S (2006) Mesenchymal stem cell-mediated functional tooth regeneration in swine. PLoS One 1:e79PubMedGoogle Scholar
  30. 30.
    Huang GT, Gronthos S, Shi S (2009) Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine. J Dent Res 88(9):792–806PubMedGoogle Scholar
  31. 31.
    Feng J, Mantesso A, De Bari C, Nishiyama A, Sharpe PT (2011) Dual origin of mesenchymal stem cells contributing to organ growth and repair. Proc Natl Acad Sci U S A 108(16):6503–6508. doi: 10.1073/pnas.1015449108 PubMedGoogle Scholar
  32. 32.
    Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS, Andriolo G, Sun B, Zheng B, Zhang L, Norotte C, Teng PN, Traas J, Schugar R, Deasy BM, Badylak S, Buhring HJ, Giacobino JP, Lazzari L, Huard J, Peault B (2008) A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3(3):301–313. doi: 10.1016/j.stem.2008.07.003 PubMedGoogle Scholar
  33. 33.
    da Silva Meirelles L, Caplan AI, Nardi NB (2008) In search of the in vivo identity of mesenchymal stem cells. Stem Cells 26(9):2287–2299PubMedGoogle Scholar
  34. 34.
    Shi S, Gronthos S (2003) Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp. J Bone Miner Res 18(4):696–704PubMedGoogle Scholar
  35. 35.
    Lapthanasupkul P, Feng J, Mantesso A, Takada-Horisawa Y, Vidal M, Koseki H, Wang L, An Z, Miletich I, Sharpe PT (2012) Ring1a/b polycomb proteins regulate the mesenchymal stem cell niche in continuously growing incisors. Dev Biol 367(2):140–153. doi: 10.1016/j.ydbio.2012.04.029 PubMedGoogle Scholar
  36. 36.
    Janebodin K, Horst OV, Ieronimakis N, Balasundaram G, Reesukumal K, Pratumvinit B, Reyes M (2011) Isolation and characterization of neural crest-derived stem cells from dental pulp of neonatal mice. PLoS One 6(11):e27526. doi: 10.1371/journal.pone.0027526 PubMedGoogle Scholar
  37. 37.
    Lovschall H, Tummers M, Thesleff I, Fuchtbauer EM, Poulsen K (2005) Activation of the notch signaling pathway in response to pulp capping of rat molars. Eur J Oral Sci 113(4):312–317. doi: 10.1111/j.1600-0722.2005.00221.x PubMedGoogle Scholar
  38. 38.
    Martens W, Wolfs E, Struys T, Politis C, Bronckaers A, Lambrichts I (2012) Expression pattern of basal markers in human dental pulp stem cells and tissue. Cells Tissues Organs 196(6):490–500. doi: 10.1159/000338654 PubMedGoogle Scholar
  39. 39.
    Sloan AJ, Smith AJ (2007) Stem cells and the dental pulp: potential roles in dentine regeneration and repair. Oral Dis 13(2):151–157PubMedGoogle Scholar
  40. 40.
    Tecles O, Laurent P, Zygouritsas S, Burger AS, Camps J, Dejou J, About I (2005) Activation of human dental pulp progenitor/stem cells in response to odontoblast injury. Arch Oral Biol 50(2):103–108PubMedGoogle Scholar
  41. 41.
    Atari M, Gil-Recio C, Fabregat M, Garcia-Fernandez D, Barajas M, Carrasco MA, Jung HS, Alfaro FH, Casals N, Prosper F, Ferres-Padro E, Giner L (2012) Dental pulp of the third molar: a new source of pluripotent-like stem cells. J Cell Sci 125(Pt 14):3343–3356. doi: 10.1242/jcs.096537 PubMedGoogle Scholar
  42. 42.
    Karbanova J, Soukup T, Suchanek J, Pytlik R, Corbeil D, Mokry J (2011) Characterization of dental pulp stem cells from impacted third molars cultured in low serum-containing medium. Cells Tissues Organs 193(6):344–365PubMedGoogle Scholar
  43. 43.
    Thesleff I, Sharpe P (1997) Signalling networks regulating dental development. Mech Dev 67(2):111–123PubMedGoogle Scholar
  44. 44.
    Thesleff I, Tummers M (2008) Tooth organogenesis and regeneration. Harvard Stem Cell Institute, CambridgeGoogle Scholar
  45. 45.
    Egusa H, Sonoyama W, Nishimura M, Atsuta I, Akiyama K (2012) Stem cells in dentistry—part I: stem cell sources. J Prosthodont Res 56(3):151–165. doi: 10.1016/j.jpor.2012.06.001 PubMedGoogle Scholar
  46. 46.
    Chen FM, Sun HH, Lu H, Yu Q (2012) Stem cell-delivery therapeutics for periodontal tissue regeneration. Biomaterials 33(27):6320–6344. doi: 10.1016/j.biomaterials.2012.05.048 PubMedGoogle Scholar
  47. 47.
    Smith AJ, Cassidy N, Perry H, Begue-Kirn C, Ruch JV, Lesot H (1995) Reactionary dentinogenesis. Int J Dev Biol 39(1):273–280PubMedGoogle Scholar
  48. 48.
    Smith AJ, Lesot H (2001) Induction and regulation of crown dentinogenesis: embryonic events as a template for dental tissue repair? Crit Rev Oral Biol Med 12(5):425–437PubMedGoogle Scholar
  49. 49.
    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(8):531–535PubMedGoogle Scholar
  50. 50.
    About I, Bottero MJ, de Denato P, Camps J, Franquin JC, Mitsiadis TA (2000) Human dentin production in vitro. Exp Cell Res 258(1):33–41PubMedGoogle Scholar
  51. 51.
    Alge DL, Zhou D, Adams LL, Wyss BK, Shadday MD, Woods EJ, Gabriel Chu TM, Goebel WS (2010) Donor-matched comparison of dental pulp stem cells and bone marrow-derived mesenchymal stem cells in a rat model. J Tissue Eng Regen Med 4(1):73–81PubMedGoogle Scholar
  52. 52.
    Shi S, Robey PG, Gronthos S (2001) Comparison of human dental pulp and bone marrow stromal stem cells by cDNA microarray analysis. Bone 29(6):532–539PubMedGoogle Scholar
  53. 53.
    Chai Y, Jiang X, Ito Y, Bringas P Jr, Han J, Rowitch DH, Soriano P, McMahon AP, Sucov HM (2000) Fate of the mammalian cranial neural crest during tooth and mandibular morphogenesis. Development 127(8):1671–1679PubMedGoogle Scholar
  54. 54.
    Graham A, Begbie J, McGonnell I (2004) Significance of the cranial neural crest. Dev Dyn 229(1):5–13PubMedGoogle Scholar
  55. 55.
    Thesleff I, Aberg T (1999) Molecular regulation of tooth development. Bone 25(1):123–125PubMedGoogle Scholar
  56. 56.
    Miletich I, Sharpe PT (2004) Neural crest contribution to mammalian tooth formation. Birth Defects Res C Embryo Today 72(2):200–212PubMedGoogle Scholar
  57. 57.
    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(6):1162–1171PubMedGoogle Scholar
  58. 58.
    Kiraly M, Kadar K, Horvathy DB, Nardai P, Racz GZ, Lacza Z, Varga G, Gerber G (2011) Integration of neuronally predifferentiated human dental pulp stem cells into rat brain in vivo. Neurochem Int 59(3):371–381PubMedGoogle Scholar
  59. 59.
    Kiraly M, Porcsalmy B, Pataki A, Kadar K, Jelitai M, Molnar B, Hermann P, Gera I, Grimm WD, Ganss B, Zsembery A, Varga G (2009) Simultaneous PKC and cAMP activation induces differentiation of human dental pulp stem cells into functionally active neurons. Neurochem Int 55(5):323–332PubMedGoogle Scholar
  60. 60.
    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(8):1394–1402PubMedGoogle Scholar
  61. 61.
    Paino F, Ricci G, De Rosa A, D'Aquino R, Laino L, Pirozzi G, Tirino V, Papaccio G (2010) Ecto-mesenchymal stem cells from dental pulp are committed to differentiate into active melanocytes. Eur Cell Mater 20:295–305PubMedGoogle Scholar
  62. 62.
    Stevens A, Zuliani T, Olejnik C, LeRoy H, Obriot H, Kerr-Conte J, Formstecher P, Bailliez Y, Polakowska RR (2008) Human dental pulp stem cells differentiate into neural crest-derived melanocytes and have label-retaining and sphere-forming abilities. Stem Cells Dev 17(6):1175–1184PubMedGoogle Scholar
  63. 63.
    Struys T, Moreels M, Martens W, Donders R, Wolfs E, Lambrichts I (2010) Ultrastructural and immunocytochemical analysis of multilineage differentiated human dental pulp- and umbilical cord-derived mesenchymal stem cells. Cells Tissues Organs 193(6):366–378PubMedGoogle Scholar
  64. 64.
    Batouli S, Miura M, Brahim J, Tsutsui TW, Fisher LW, Gronthos S, Robey PG, Shi S (2003) Comparison of stem-cell-mediated osteogenesis and dentinogenesis. J Dent Res 82(12):976–981PubMedGoogle Scholar
  65. 65.
    Huang GT, Yamaza T, Shea LD, Djouad F, Kuhn NZ, Tuan RS, Shi S (2010) Stem/progenitor cell-mediated de novo regeneration of dental pulp with newly deposited continuous layer of dentin in an in vivo model. Tissue Eng 16(2):605–615Google Scholar
  66. 66.
    Marchionni C, Bonsi L, Alviano F, Lanzoni G, Di Tullio A, Costa R, Montanari M, Tazzari PL, Ricci F, Pasquinelli G, Orrico C, Grossi A, Prati C, Bagnara GP (2009) Angiogenic potential of human dental pulp stromal (stem) cells. Int J Immunopathol Pharmacol 22(3):699–706PubMedGoogle Scholar
  67. 67.
    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(3):638–645PubMedGoogle Scholar
  68. 68.
    Nakashima M, Iohara K, Sugiyama M (2009) Human dental pulp stem cells with highly angiogenic and neurogenic potential for possible use in pulp regeneration. Cytokine Growth Factor Rev 20(5–6):435–440PubMedGoogle Scholar
  69. 69.
    Arthur A, Rychkov G, Shi S, Koblar SA, Gronthos S (2008) Adult human dental pulp stem cells differentiate toward functionally active neurons under appropriate environmental cues. Stem Cells 26(7):1787–1795PubMedGoogle Scholar
  70. 70.
    Arthur A, Shi S, Zannettino AC, Fujii N, Gronthos S, Koblar SA (2009) Implanted adult human dental pulp stem cells induce endogenous axon guidance. Stem Cells 27(9):2229–2237PubMedGoogle Scholar
  71. 71.
    Nosrat IV, Smith CA, Mullally P, Olson L, Nosrat CA (2004) Dental pulp cells provide neurotrophic support for dopaminergic neurons and differentiate into neurons in vitro; implications for tissue engineering and repair in the nervous system. Eur J Neurosci 19(9):2388–2398PubMedGoogle Scholar
  72. 72.
    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(1):120–132PubMedGoogle Scholar
  73. 73.
    Yalvac ME, Rizvanov AA, Kilic E, Sahin F, Mukhamedyarov MA, Islamov RR, Palotas A (2009) Potential role of dental stem cells in the cellular therapy of cerebral ischemia. Curr Pharm Des 15(33):3908–3916PubMedGoogle Scholar
  74. 74.
    Papaccio G, Graziano A, d'Aquino R, Graziano MF, Pirozzi G, Menditti D, De Rosa A, Carinci F, Laino G (2006) Long-term cryopreservation of dental pulp stem cells (SBP-DPSCs) and their differentiated osteoblasts: a cell source for tissue repair. J Cell Physiol 208(2):319–325PubMedGoogle Scholar
  75. 75.
    Perry BC, Zhou D, Wu X, Yang FC, Byers MA, Chu TM, Hockema JJ, Woods EJ, Goebel WS (2008) Collection, cryopreservation, and characterization of human dental pulp-derived mesenchymal stem cells for banking and clinical use. Tissue Eng Part C Methods 14(2):149–156PubMedGoogle Scholar
  76. 76.
    Zhang W, Walboomers XF, Shi S, Fan M, Jansen JA (2006) Multilineage differentiation potential of stem cells derived from human dental pulp after cryopreservation. Tissue Eng 12(10):2813–2823PubMedGoogle Scholar
  77. 77.
    Bakopoulou A, Leyhausen G, Volk J, Tsiftsoglou A, Garefis P, Koidis P, Geurtsen W (2011) Assessment of the impact of two different isolation methods on the osteo/odontogenic differentiation potential of human dental stem cells derived from deciduous teeth. Calcif Tissue Int 88(2):130–141PubMedGoogle Scholar
  78. 78.
    Kerkis I, Kerkis A, Dozortsev D, Stukart-Parsons GC, Gomes Massironi SM, Pereira LV, Caplan AI, Cerruti HF (2006) Isolation and characterization of a population of immature dental pulp stem cells expressing OCT-4 and other embryonic stem cell markers. Cells Tissues Organs 184(3–4):105–116PubMedGoogle Scholar
  79. 79.
    Wang J, Wang X, Sun Z, Wang X, Yang H, Shi S, Wang S (2010) Stem cells from human-exfoliated deciduous teeth can differentiate into dopaminergic neuron-like cells. Stem Cells Dev 19(9):1375–1383PubMedGoogle Scholar
  80. 80.
    Sakai VT, Zhang Z, Dong Z, Neiva KG, Machado MA, Shi S, Santos CF, Nor JE (2010) SHED differentiate into functional odontoblasts and endothelium. J Dent Res 89(8):791–796PubMedGoogle Scholar
  81. 81.
    Gay IC, Chen S, MacDougall M (2007) Isolation and characterization of multipotent human periodontal ligament stem cells. Orthod Craniofac Res 10(3):149–160PubMedGoogle Scholar
  82. 82.
    Xu J, Wang W, Kapila Y, Lotz J, Kapila S (2009) Multiple differentiation capacity of STRO-1+/CD146+ PDL mesenchymal progenitor cells. Stem Cells Dev 18(3):487–496PubMedGoogle Scholar
  83. 83.
    Techawattanawisal W, Nakahama K, Komaki M, Abe M, Takagi Y, Morita I (2007) Isolation of multipotent stem cells from adult rat periodontal ligament by neurosphere-forming culture system. Biochem Biophys Res Commun 357(4):917–923PubMedGoogle Scholar
  84. 84.
    Liu Y, Zheng Y, Ding G, Fang D, Zhang C, Bartold PM, Gronthos S, Shi S, Wang S (2008) Periodontal ligament stem cell-mediated treatment for periodontitis in miniature swine. Stem Cells 26(4):1065–1073PubMedGoogle Scholar
  85. 85.
    Morsczeck C, Vollner F, Saugspier M, Brandl C, Reichert TE, Driemel O, Schmalz G (2010) Comparison of human dental follicle cells (DFCs) and stem cells from human exfoliated deciduous teeth (SHED) after neural differentiation in vitro. Clin Oral Investig 14(4):433–440PubMedGoogle Scholar
  86. 86.
    Yao S, Pan F, Prpic V, Wise GE (2008) Differentiation of stem cells in the dental follicle. J Dent Res 87(8):767–771PubMedGoogle Scholar
  87. 87.
    Yokoi T, Saito M, Kiyono T, Iseki S, Kosaka K, Nishida E, Tsubakimoto T, Harada H, Eto K, Noguchi T, Teranaka T (2007) Establishment of immortalized dental follicle cells for generating periodontal ligament in vivo. Cell Tissue Res 327(2):301–311PubMedGoogle Scholar
  88. 88.
    D'Souza R (2002) Development of the pulpodentin complex. In: Kenneth M, Hargreaves HEG (eds) Seltzer and Bender's dental pulp. Quintessence, Carol StreamGoogle Scholar
  89. 89.
    Bakopoulou A, Leyhausen G, Volk J, Tsiftsoglou A, Garefis P, Koidis P, Geurtsen W (2011) Comparative analysis of in vitro osteo/odontogenic differentiation potential of human dental pulp stem cells (DPSCs) and stem cells from the apical papilla (SCAP). Arch Oral Biol 56(7):709–721. doi: 10.1016/j.archoralbio.2010.12.008 PubMedGoogle Scholar
  90. 90.
    Abe S, Yamaguchi S, Amagasa T (2007) Multilineage cells from apical pulp of human tooth with immature apex. Oral Sci Int 4:45–58Google Scholar
  91. 91.
    Chueh LH, Huang GT (2006) Immature teeth with periradicular periodontitis or abscess undergoing apexogenesis: a paradigm shift. J Endod 32(12):1205–1213PubMedGoogle Scholar
  92. 92.
    Huang GT, Sonoyama W, Liu Y, Liu H, Wang S, Shi S (2008) The hidden treasure in apical papilla: the potential role in pulp/dentin regeneration and bioroot engineering. J Endod 34(6):645–651PubMedGoogle Scholar
  93. 93.
    Wislet-Gendebien S, Hans G, Leprince P, Rigo JM, Moonen G, Rogister B (2005) Plasticity of cultured mesenchymal stem cells: switch from nestin-positive to excitable neuron-like phenotype. Stem Cells 23(3):392–402PubMedGoogle Scholar
  94. 94.
    Wislet-Gendebien S, Leprince P, Moonen G, Rogister B (2003) Regulation of neural markers nestin and GFAP expression by cultivated bone marrow stromal cells. J Cell Sci 116(Pt 16):3295–3302PubMedGoogle Scholar
  95. 95.
    Woodbury D, Schwarz EJ, Prockop DJ, Black IB (2000) Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res 61(4):364–370PubMedGoogle Scholar
  96. 96.
    Ma K, Fox L, Shi G, Shen J, Liu Q, Pappas JD, Cheng J, Qu T (2011) Generation of neural stem cell-like cells from bone marrow-derived human mesenchymal stem cells. Neurol Res 33(10):1083–1093. doi: 10.1179/1743132811Y.0000000053 PubMedGoogle Scholar
  97. 97.
    Kitada M (2012) Mesenchymal cell populations: development of the induction systems for Schwann cells and neuronal cells and finding the unique stem cell population. Anat Sci Int 87(1):24–44. doi: 10.1007/s12565-011-0128-4 PubMedGoogle Scholar
  98. 98.
    Maltman DJ, Hardy SA, Przyborski SA (2011) Role of mesenchymal stem cells in neurogenesis and nervous system repair. Neurochem Int 59(3):347–356. doi: 10.1016/j.neuint.2011.06.008 PubMedGoogle Scholar
  99. 99.
    Struys T, Moreels M, Martens W, Donders R, Wolfs E, Lambrichts I (2011) Ultrastructural and immunocytochemical analysis of multilineage differentiated human dental pulp- and umbilical cord-derived mesenchymal stem cells. Cells Tissues Organs 193(6):366–378. doi: 10.1159/000321400 PubMedGoogle Scholar
  100. 100.
    De Miguel MP, Fuentes-Julian S, Blazquez-Martinez A, Pascual CY, Aller MA, Arias J, Arnalich-Montiel F (2012) Immunosuppressive properties of mesenchymal stem cells: advances and applications. Curr Mol Med 12(5):574–591PubMedGoogle Scholar
  101. 101.
    Nauta AJ, Fibbe WE (2007) Immunomodulatory properties of mesenchymal stromal cells. Blood 110(10):3499–3506. doi: 10.1182/blood-2007-02-069716 PubMedGoogle Scholar
  102. 102.
    Ding G, Liu Y, An Y, Zhang C, Shi S, Wang W, Wang S (2010) Suppression of T cell proliferation by root apical papilla stem cells in vitro. Cells Tissues Organs 191(5):357–364. doi: 10.1159/000276589 PubMedGoogle Scholar
  103. 103.
    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 GP (2005) Multipotent mesenchymal stem cells with immunosuppressive activity can be easily isolated from dental pulp. Transplantation 80(6):836–842PubMedGoogle Scholar
  104. 104.
    Tomic S, Djokic J, Vasilijic S, Vucevic D, Todorovic V, Supic G, Colic M (2011) Immunomodulatory properties of mesenchymal stem cells derived from dental pulp and dental follicle are susceptible to activation by toll-like receptor agonists. Stem Cells Dev 20(4):695–708. doi: 10.1089/scd.2010.0145 PubMedGoogle Scholar
  105. 105.
    Wada N, Menicanin D, Shi S, Bartold PM, Gronthos S (2009) Immunomodulatory properties of human periodontal ligament stem cells. J Cell Physiol 219(3):667–676. doi: 10.1002/jcp.21710 PubMedGoogle Scholar
  106. 106.
    Yamaza T, Kentaro A, Chen C, Liu Y, Shi Y, Gronthos S, Wang S, Shi S (2010) Immunomodulatory properties of stem cells from human exfoliated deciduous teeth. Stem Cell Res Ther 1(1):5. doi: 10.1186/scrt5 PubMedGoogle Scholar
  107. 107.
    Karaoz E, Dogan BN, Aksoy A, Gacar G, Akyuz S, Ayhan S, Genc ZS, Yuruker S, Duruksu G, Demircan PC, Sariboyaci AE (2010) Isolation and in vitro characterisation of dental pulp stem cells from natal teeth. Histochem Cell Biol 133(1):95–112PubMedGoogle Scholar
  108. 108.
    Huang AH, Snyder BR, Cheng PH, Chan AW (2008) Putative dental pulp-derived stem/stromal cells promote proliferation and differentiation of endogenous neural cells in the hippocampus of mice. Stem Cells 26(10):2654–2663PubMedGoogle Scholar
  109. 109.
    Sasaki R, Aoki S, Yamato M, Uchiyama H, Wada K, Okano T, Ogiuchi H (2008) Neurosphere generation from dental pulp of adult rat incisor. Eur J Neurosci 27(3):538–548PubMedGoogle Scholar
  110. 110.
    Kadar K, Kiraly M, Porcsalmy B, Molnar B, Racz GZ, Blazsek J, Kallo K, Szabo EL, Gera I, Gerber G, Varga G (2009) Differentiation potential of stem cells from human dental origin—promise for tissue engineering. J Physiol Pharmacol 60(Suppl 7):167–175PubMedGoogle Scholar
  111. 111.
    Osathanon T, Nowwarote N, Pavasant P (2011) Basic fibroblast growth factor inhibits mineralization but induces neuronal differentiation by human dental pulp stem cells through a FGFR and PLCgamma signaling pathway. J Cell Biochem 112(7):1807–1816PubMedGoogle Scholar
  112. 112.
    Apel C, Forlenza OV, de Paula VJ, Talib LL, Denecke B, Eduardo CP, Gattaz WF (2009) The neuroprotective effect of dental pulp cells in models of Alzheimer's and Parkinson's disease. J Neural Transm 116(1):71–78PubMedGoogle Scholar
  113. 113.
    de Almeida FM, Marques SA, Ramalho Bdos S, Rodrigues RF, Cadilhe DV, Furtado D, Kerkis I, Pereira LV, Rehen SK, Martinez AM (2011) Human dental pulp cells: a new source of cell therapy in a mouse model of compressive spinal cord injury. J Neurotrauma 28(9):1939–1949. doi: 10.1089/neu.2010.1317 PubMedGoogle Scholar
  114. 114.
    Struys T, Ketkar-Atre A, Gervois P, Leten C, Hilkens P, Martens W, Bronckaers A, Dresselaers T, Politis C, Lambrichts I, Himmelreich U (2012) Magnetic resonance imaging of human dental pulp stem cells in vitro and in vivo. Cell Transplant. doi: 10.3727/096368912X657774 PubMedGoogle Scholar
  115. 115.
    Sasaki R, Aoki S, Yamato M, Uchiyama H, Wada K, Ogiuchi H, Okano T, Ando T (2011) PLGA artificial nerve conduits with dental pulp cells promote facial nerve regeneration. J Tissue Eng Regen Med. doi: 10.1002/term.387 Google Scholar
  116. 116.
    Kress B, Gottschalk A, Anders L, Stippich C, Palm F, Bahren W, Sartor K (2004) High-resolution dental magnetic resonance imaging of inferior alveolar nerve responses to the extraction of third molars. Eur Radiol 14(8):1416–1420PubMedGoogle Scholar
  117. 117.
    Valmaseda-Castellon E, Berini-Aytes L, Gay-Escoda C (2001) Inferior alveolar nerve damage after lower third molar surgical extraction: a prospective study of 1117 surgical extractions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 92(4):377–383PubMedGoogle Scholar
  118. 118.
    Alhassani AA, AlGhamdi AS (2010) Inferior alveolar nerve injury in implant dentistry: diagnosis, causes, prevention, and management. J Oral Implantol 36(5):401–407PubMedGoogle Scholar
  119. 119.
    Erbay SH, Bhadelia RA, O'Callaghan M, Gupta P, Riesenburger R, Krackov W, Polak JF (2006) Nerve atrophy in severe trigeminal neuralgia: noninvasive confirmation at MR imaging–initial experience. Radiology 238(2):689–692PubMedGoogle Scholar
  120. 120.
    Smith MH, Lung KE (2006) Nerve injuries after dental injection: a review of the literature. J Can Dent Assoc 72(6):559–564PubMedGoogle Scholar
  121. 121.
    Jones RH (2010) The use of vein grafts in the repair of the inferior alveolar nerve following surgery. Aust Dent J 55(2):207–213PubMedGoogle Scholar
  122. 122.
    Satar B, Karahatay S, Kurt B, Ural AU, Safali M, Avcu F, Oztas E, Kucuktag Z (2009) Repair of transected facial nerve with mesenchymal stromal cells: histopathologic evidence of superior outcome. Laryngoscope 119(11):2221–2225PubMedGoogle Scholar
  123. 123.
    Atsumi Y, Imai T, Matsumoto K, Sakuda M, Maeda T, Kurisu K, Wakisaka S (2000) Effects of different types of injury to the inferior alveolar nerve on the behavior of Schwann cells during the regeneration of periodontal nerve fibers of rat incisor. Arch Histol Cytol 63(1):43–54PubMedGoogle Scholar
  124. 124.
    Tohill M, Mantovani C, Wiberg M, Terenghi G (2004) Rat bone marrow mesenchymal stem cells express glial markers and stimulate nerve regeneration. Neurosci Lett 362(3):200–203PubMedGoogle Scholar
  125. 125.
    Walsh S, Midha R (2009) Practical considerations concerning the use of stem cells for peripheral nerve repair. Neurosurg Focus 26(2):E2PubMedGoogle Scholar
  126. 126.
    Brohlin M, Mahay D, Novikov LN, Terenghi G, Wiberg M, Shawcross SG, Novikova LN (2009) Characterisation of human mesenchymal stem cells following differentiation into Schwann cell-like cells. Neurosci Res 64(1):41–49PubMedGoogle Scholar
  127. 127.
    Caddick J, Kingham PJ, Gardiner NJ, Wiberg M, Terenghi G (2006) Phenotypic and functional characteristics of mesenchymal stem cells differentiated along a Schwann cell lineage. Glia 54(8):840–849PubMedGoogle Scholar
  128. 128.
    Dezawa M, Takahashi I, Esaki M, Takano M, Sawada H (2001) Sciatic nerve regeneration in rats induced by transplantation of in vitro differentiated bone-marrow stromal cells. Eur J Neurosci 14(11):1771–1776PubMedGoogle Scholar
  129. 129.
    Keilhoff G, Goihl A, Langnase K, Fansa H, Wolf G (2006) Transdifferentiation of mesenchymal stem cells into Schwann cell-like myelinating cells. Eur J Cell Biol 85(1):11–24PubMedGoogle Scholar
  130. 130.
    Ladak A, Olson J, Tredget EE, Gordon T (2011) Differentiation of mesenchymal stem cells to support peripheral nerve regeneration in a rat model. Exp Neurol 228(2):242–252PubMedGoogle Scholar
  131. 131.
    Lin W, Chen X, Wang X, Liu J, Gu X (2008) Adult rat bone marrow stromal cells differentiate into Schwann cell-like cells in vitro. In Vitro Cell Dev Biol 44(1–2):31–40Google Scholar
  132. 132.
    Mimura T, Dezawa M, Kanno H, Sawada H, Yamamoto I (2004) Peripheral nerve regeneration by transplantation of bone marrow stromal cell-derived Schwann cells in adult rats. J Neurosurg 101(5):806–812PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • W. Martens
    • 1
  • A. Bronckaers
    • 1
  • C. Politis
    • 1
    • 2
  • R. Jacobs
    • 3
  • I. Lambrichts
    • 1
  1. 1.Biomedical Research Institute, Laboratory of MorphologyHasselt UniversityDiepenbeekBelgium
  2. 2.Department of oral and Maxillofacial SurgeryKU LeuvenLeuvenBelgium
  3. 3.Oral Imaging Center, Department of Dentistry, Oral Pathology and Maxillofacial Surgery, Faculty of MedicineKU LeuvenLeuvenBelgium

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