Dental Pulp Stem Cell Niche

  • Jinhua Yu
  • Mohamed Jamal
  • Franklin Garcia-Godoy
  • George T.-J. Huang
Chapter
First Online:
Part of the Stem Cell Biology and Regenerative Medicine book series (STEMCELL)

Abstract

Dental stem cells exist in dental tissues. Of those that have been isolated and better studied are those reside in dental pulp. These dental tissue-derived mesenchymal stem/stromal cells (MSCs) shared similar characteristics to other MSCs , yet, they are subtly different. The markers to identify MSC populations in situ as well as after isolation into cell cultures have been elusive. A number of markers have been used to identify dental pulp stem cells (DPSCs ) in situ such as STRO-1 , CD146 , 3G5, NOTCH3 and NG2 . Certain subpopulations based on some marker expression have been studied in vitro and tested for pulp-dentin tissue regeneration. Various approaches have been utilized to study the cellular and molecular mechanisms involved in the DPSC interactions with its niche components such as extracellular matrix . This chapter will focus on the review of the recent studies regarding DPSC niches and particularly their regulation.

Keywords

Dental stem cells Niche Stemness Pluripotent genes DPSCs SCAP MSCs STRO-1 CD146 NG2 NOTCH3 Growth factors Extracellular matrix ECM Signaling pathways 

Abbreviations

DPSCs

Dental pulp stem cells

SHED

Stem cells from exfoliated deciduous teeth

PDLSCs

Periodontal ligament stem cells

DFPCs

Dental follicle precursor cells

SCAP

Stem cells from apical papilla

MSCs

Mesenchymal stromal/stem cells

BMMSCs

Bone marrow stromal/stem cells

ECM

Extracellular matrix

HA/TCP

Hydroxyapatite/tricalcium phosphate

LAB

Living autologous fibrous bone

SBP/DPSCs

Stromal bone producing DPSCs

MDPSCs

Mobilized DPSCs

PLLA

Poly-L-lactic acid

HA-PCL

Hydroxyapatite-polycaprolactone

nHA

Nano-hydroxyapatite

DSPP

Dentin sialophosphoprotein

DSP

Dentin sialoprotein

DPP

Dentin phosphoprotein

DMP-1

Dentin matrix protein-1

BMPs

Bone morphogenetic proteins

FGFs

Fibroblast growth factors

VEGF

Vascular endothelial growth factor

IGFs

Insulin-like growth factors

TGF-β

Transforming growth factor

PDGF

Platelet-derived growth factor

EGF

Epidermal growth factor

FKBP1A

FK506 binding protein 1A

OPN

Osteopontin

MAPK

Mitogen-activated protein kinases

ERK

Extracellular signal-regulated kinases

JNK

c-Jun-N-terminal kinase

SP

Side population

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Notes

Acknowledgments

This work was supported in part by grants from the National Institutes of Health R01 DE019156 (G.T.-J.H.).

References

  1. 1.
    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 U S A. 2000;97(25):13625–30.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    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. 2003;100(10):5807–12.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    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.PubMedCrossRefGoogle Scholar
  4. 4.
    Morsczeck C, Gotz W, Schierholz J, Zeilhofer F, Kuhn U, Mohl C, et al. Isolation of precursor cells (PCs) from human dental follicle of wisdom teeth. Matrix Biol. 2005;24(2):155–65.PubMedCrossRefGoogle Scholar
  5. 5.
    Sonoyama W, Liu Y, Fang D, Yamaza T, Seo BM, Zhang C, et al. Mesenchymal stem cell-mediated functional tooth regeneration in Swine. PLoS One. 2006;1:e79.Google Scholar
  6. 6.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    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.PubMedCrossRefGoogle Scholar
  8. 8.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Gronthos S, Brahim J, Li W, Fisher LW, Cherman N, Boyde A, et al. Stem cell properties of human dental pulp stem cells. J Dent Res. 2002;81(8):531–5.PubMedCrossRefGoogle Scholar
  10. 10.
    Zhang W, Walboomers XF, Shi S, Fan M, Jansen JA. Multilineage differentiation potential of stem cells derived from human dental pulp after cryopreservation. Tissue Eng. 2006;12(10):2813–23.PubMedCrossRefGoogle Scholar
  11. 11.
    Batouli S, Miura M, Brahim J, Tsutsui TW, Fisher LW, Gronthos S, et al. Comparison of stem-cell-mediated osteogenesis and dentinogenesis. J Dent Res. 2003;82(12):976–81.PubMedCrossRefGoogle Scholar
  12. 12.
    Gronthos S, Graves SE, Ohta S, Simmons PJ. The STRO-1+ fraction of adult human bone marrow contains the osteogenic precursors. Blood. 1994;84(12):4164–73.PubMedGoogle Scholar
  13. 13.
    Huang GTJ, Yamaza T, Shea LD, Djouad F, Kuhn NZ, Tuan RS, et al. Stem/progenitor cell–mediated de novo regeneration of dental pulp with newly deposited continuous layer of dentin in an in vivo model. Tissue Eng Part A. 2009;16(2):605–15.PubMedCentralCrossRefGoogle Scholar
  14. 14.
    Banchs F, Trope M. Revascularization of immature permanent teeth with apical periodontitis: new treatment protocol? J Endod. 2004;30(4):196–200.PubMedCrossRefGoogle Scholar
  15. 15.
    Huang GTJ, Sonoyama W, Liu Y, Liu H, Wang S, Shi S. The hidden treasure in apical papilla: the potential role in pulp/dentin regeneration and bioroot engineering. J Endod. 2008;34(6):645–51.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Moore KA, Lemischka IR. Stem cells and their niches. Science. 2006;311(5769):1880–5.PubMedCrossRefGoogle Scholar
  17. 17.
    Roeder I, Loeffler M, Glauche I. Towards a quantitative understanding of stem cell–niche interaction: Experiments, models, and technologies. Blood Cells Mol Dis. 2011;46(4):308–17.PubMedCrossRefGoogle Scholar
  18. 18.
    Schofield R. The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells. 1978;4(1–2):7–25.PubMedGoogle Scholar
  19. 19.
    Crisan M, Yap S, Casteilla L, Chen C-W, 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.PubMedCrossRefGoogle Scholar
  20. 20.
    Ergun S, Tilki D, Klein D. Vascular wall as a reservoir for different types of stem and progenitor cells. Antioxid Redox Signal. 2011;15(4):981–95.PubMedCrossRefGoogle Scholar
  21. 21.
    Shi S, Gronthos S. Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp. J Bone Miner Res. 2003;18(4):696–704.PubMedCrossRefGoogle Scholar
  22. 22.
    Martens W, Wolfs E, Struys T, Politis C, Bronckaers A, Lambrichts I. Expression pattern of basal markers in human dental pulp stem cells and tissue. Cells Tissues Organs. 2012;196(6):490–500.PubMedCrossRefGoogle Scholar
  23. 23.
    Martel-Pelletier J, Lajeunesse D, Reboul P, Pelletier JP. Therapeutic role of dual inhibitors of 5-LOX and COX, selective and non-selective non-steroidal anti-inflammatory drugs. Ann Rheum Dis. 2003;62(6):501–9.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Greco SJ, Liu K, Rameshwar P. Functional similarities among genes regulated by OCT4 in human mesenchymal and embryonic stem cells. Stem Cells. 2007;25(12):3143–54.PubMedCrossRefGoogle Scholar
  25. 25.
    Pierantozzi E, Gava B, Manini I, Roviello F, Marotta G, Chiavarelli M, et al. Pluripotency regulators in human mesenchymal stem cells: expression of NANOG but not of OCT-4 and SOX-2. Stem Cells Devel. 2011;20(5):915–23.CrossRefGoogle Scholar
  26. 26.
    Lizier NF, Kerkis A, Gomes CM, Hebling J, Oliveira CF, Caplan AI, et al. Scaling-up of dental pulp stem cells isolated from multiple niches. PLoS ONE. 2012;7(6):e39885.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Al-Habib M, Yu Z, Huang GT. Small molecules affect human dental pulp stem cell properties via multiple signaling pathways. Stem Cells Dev. 2013;22(17):2402–13.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Jiang L, Zhu YQ, Du R, Gu YX, Xia L, Qin F, et al. The expression and role of stromal cell-derived factor-1alpha-CXCR4 axis in human dental pulp. J Endod. 2008;34(8):939–44.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Jiang H, Ling J, Gong Q. The expression of stromal cell-derived factor 1 (SDF-1) in inflamed human dental pulp. J Endod. 2008;34(11):1351–4.PubMedCrossRefGoogle Scholar
  30. 30.
    Lovschall H, Mitsiadis TA, Poulsen K, Jensen KH, Kjeldsen AL. Coexpression of Notch3 and Rgs5 in the pericyte-vascular smooth muscle cell axis in response to pulp injury. Int J Dev Biol. 2007;51(8):715–21.PubMedCrossRefGoogle Scholar
  31. 31.
    Mitsiadis TA, Feki A, Papaccio G, Caton J. Dental pulp stem cells, niches, and Notch signaling in tooth injury. Adv Dent Res. 2011;23(3):275–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Kaukua N, Shahidi MK, Konstantinidou C, Dyachuk V, Kaucka M, Furlan A, et al. Glial origin of mesenchymal stem cells in a tooth model system. Nature. 2014;513(7519):551–4.PubMedCrossRefGoogle Scholar
  33. 33.
    Feng J, Mantesso A, De Bari C, Nishiyama A, Sharpe PT. Dual origin of mesenchymal stem cells contributing to organ growth and repair. Proc Natl Acad Sci U S A. 2011;108(16):6503–8.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Abe S, Yamaguchi S, Amagasa T. Multilineage cells from apical pulp of human tooth with immature apex. Oral Sci Int. 2007;4(1):45–58. CrossRefGoogle Scholar
  35. 35.
    Jamal M, Chogle SM, Karam SM, Huang GT. NOTCH3 is expressed in human apical papilla and in subpopulations of stem cells isolated from the tissue. Genes Dis. 2015 [E-pub].Google Scholar
  36. 36.
    Liu JY, Chen X, Yue L, Huang GT, Zou XY. CXC chemokine receptor 4 is expressed paravascularly in apical papilla and coordinates with stromal cell-derived factor-1alpha during transmigration of stem cells from apical papilla. J Endod. 2015 [E-pub].Google Scholar
  37. 37.
    Yang X, van den Dolder J, Walboomers XF, Zhang W, Bian Z, Fan M, et al. The odontogenic potential of STRO-1 sorted rat dental pulp stem cells in vitro. J Tissue Eng Regen Med. 2007;1(1):66–73.PubMedCrossRefGoogle Scholar
  38. 38.
    Yang X, Zhang W, van den Dolder J, Walboomers XF, Bian Z, Fan M, et al. Multilineage potential of STRO-1+ rat dental pulp cells in vitro. J Tissue Eng Regen Med. 2007;1(2):128–35.PubMedCrossRefGoogle Scholar
  39. 39.
    Laino G, d’Aquino R, Graziano A, Lanza V, Carinci F, Naro F, et al. A new population of human adult dental pulp stem cells: a useful source of living autologous fibrous bone tissue (LAB). J Bone Miner Res. 2005;20(8):1394–402.PubMedCrossRefGoogle Scholar
  40. 40.
    Lin CS, Ning H, Lin G, Lue TF. Is CD34 truly a negative marker for mesenchymal stromal cells? Cytotherapy. 2012;14(10):1159–63.PubMedCrossRefGoogle Scholar
  41. 41.
    Lin CS, Xin ZC, Dai J, Lue TF. Commonly used mesenchymal stem cell markers and tracking labels: limitations and challenges. Histol Histopathol. 2013;28(9):1109–16.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Laino G, Graziano A, d’Aquino R, Pirozzi G, Lanza V, Valiante S, et al. An approachable human adult stem cell source for hard-tissue engineering. J Cell Physiol. 2006;206(3):693–701.PubMedCrossRefGoogle Scholar
  43. 43.
    Iohara K, Zheng L, Ito M, Tomokiyo A, Matsushita K, Nakashima M. Side population cells isolated from porcine dental pulp tissue with self-renewal and multipotency for dentinogenesis, chondrogenesis, adipogenesis, and neurogenesis. Stem Cells. 2006;24(11):2493–503.PubMedCrossRefGoogle Scholar
  44. 44.
    Iohara K, Zheng L, Wake H, Ito M, Nabekura J, Wakita H, et al. A novel stem cell source for vasculogenesis in ischemia: subfraction of side population cells from dental pulp. Stem Cells. 2008;26(9):2408–18.PubMedCrossRefGoogle Scholar
  45. 45.
    Sugiyama M, Iohara K, Wakita H, Hattori H, Ueda M, Matsushita K, et al. Dental pulp-derived CD31/CD146 side population stem/progenitor cells enhance recovery of focal cerebral ischemia in rats. Tissue Eng Part A. 2011;17(9–10):1303–11.PubMedCrossRefGoogle Scholar
  46. 46.
    Iohara K, Imabayashi K, Ishizaka R, Watanabe A, Nabekura J, Ito M, et al. Complete pulp regeneration after pulpectomy by transplantation of CD105+ stem cells with stromal cell-derived factor-1. Tissue Eng Part A. 2011;17(15–16):1911–20.PubMedCrossRefGoogle Scholar
  47. 47.
    Iohara K, Zheng L, Ito M, Ishizaka R, Nakamura H, Into T, et al. Regeneration of dental pulp after pulpotomy by transplantation of CD31(-)/CD146(-) side population cells from a canine tooth. Regen Med. 2009;4(3):377–85.PubMedCrossRefGoogle Scholar
  48. 48.
    Iohara K, Murakami M, Takeuchi N, Osako Y, Ito M, Ishizaka R, et al. A novel combinatorial therapy with pulp stem cells and granulocyte colony-stimulating factor for total pulp regeneration. Stem Cells Transl Med. 2013;2(7):521–33.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Nakashima M, Iohara K, Murakami M. Dental pulp stem cells and regeneration. Endod Top. 2013;28(1):38–50.CrossRefGoogle Scholar
  50. 50.
    Kawanabe N, Murata S, Fukushima H, Ishihara Y, Yanagita T, Yanagita E, et al. Stage-specific embryonic antigen-4 identifies human dental pulp stem cells. Exp Cell Res. 2012;318(5):453–63.PubMedCrossRefGoogle Scholar
  51. 51.
    Hynes RO. The extracellular matrix: not just pretty fibrils. Science. 2009;326(5957):1216–9.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Fuchs E, Tumbar T, Guasch G. Socializing with the neighbors: stem cells and their niche. Cell. 2004;116(6):769–78.PubMedCrossRefGoogle Scholar
  53. 53.
    Brizzi MF, Tarone G, Defilippi P. Extracellular matrix, integrins, and growth factors as tailors of the stem cell niche. Curr Opin Cell Biol. 2012;24(5):645–51.PubMedCrossRefGoogle Scholar
  54. 54.
    Discher DE, Mooney DJ, Zandstra PW. Growth factors, matrices, and forces combine and control stem cells. Science. 2009;324(5935):1673–7.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Kurtz A, Oh SJ. Age related changes of the extracellular matrix and stem cell maintenance. Prev Med 2012;54 Suppl:S50–S56.Google Scholar
  56. 56.
    Engler AJ, Sen S, Sweeney HL, Discher DE. Matrix elasticity directs stem cell lineage specification. Cell. 2006;126(4):677–89.PubMedCrossRefGoogle Scholar
  57. 57.
    Alessandri M, Lizzo G, Gualandi C, Mangano C, Giuliani A, Focarete ML, et al. Influence of biological matrix and artificial electrospun scaffolds on proliferation, differentiation and trophic factor synthesis of rat embryonic stem cells. Matrix Biol. 2014;33:68–76.Google Scholar
  58. 58.
    D’Anto V, Raucci MG, Guarino V, Martina S, Valletta R, Ambrosio L. Behaviour of human mesenchymal stem cells on chemically synthesized HA-PCL scaffolds for hard tissue regeneration. J Tissue Eng Regen Med. 2013.Google Scholar
  59. 59.
    Collart-Dutilleul PY, Secret E, Panayotov I, Deville de Periere D, Martin-Palma RJ, Torres-Costa V, et al. Adhesion and proliferation of human mesenchymal stem cells from dental pulp on porous silicon scaffolds. ACS Appl Mater Interfaces. 2014;6(3):1719–28.PubMedCrossRefGoogle Scholar
  60. 60.
    Yang X, Yang F, Walboomers XF, Bian Z, Fan M, Jansen JA. The performance of dental pulp stem cells on nanofibrous PCL/gelatin/nHA scaffolds. J Biomed Mater Res Part A. 2010;93(1):247–57.Google Scholar
  61. 61.
    Yu J, Shi J, Jin Y. Current approaches and challenges in making a bio-tooth. Tissue Eng Part B Rev. 2008;14(3):307–19.PubMedCrossRefGoogle Scholar
  62. 62.
    Even-Ram S, Artym V, Yamada KM. Matrix control of stem cell fate. Cell. 2006;126(4):645–7.PubMedCrossRefGoogle Scholar
  63. 63.
    Zhang W, Walboomers XF, van Kuppevelt TH, Daamen WF, Bian Z, Jansen JA. The performance of human dental pulp stem cells on different three-dimensional scaffold materials. Biomaterials. 2006;27(33):5658–68.PubMedCrossRefGoogle Scholar
  64. 64.
    Nemeth CL, Janebodin K, Yuan AE, Dennis JE, Reyes M, Kim DH. Enhanced chondrogenic differentiation of dental pulp stem cells using nanopatterned PEG-GelMA-HA hydrogels. Tissue Eng Part A. 2014;20(21–22):2817–29.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Huang B, Sun Y, Maciejewska I, Qin D, Peng T, McIntyre B, et al. Distribution of SIBLING proteins in the organic and inorganic phases of rat dentin and bone. Eur J Oral Sci. 2008;116(2):104–12.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Zhang YD, Chen Z, Song YQ, Liu C, Chen YP. Making a tooth: growth factors, transcription factors, and stem cells. Cell Res. 2005;15(5):301–16.PubMedCrossRefGoogle Scholar
  67. 67.
    Nagatomo KJ, Tompkins KA, Fong H, Zhang H, Foster BL, Chu EY, et al. Transgenic overexpression of gremlin results in developmental defects in enamel and dentin in mice. Connect Tissue Res. 2008;49(6):391–400.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Liu HC, E LL, Wang DS, Su F, Wu X, Shi ZP, et al. Reconstruction of alveolar bone defects using bone morphogenetic protein 2 mediated rabbit dental pulp stem cells seeded on nano-hydroxyapatite/collagen/poly(L-lactide). Tissue Eng Part A. 2011;17(19–20):2417–2433.Google Scholar
  69. 69.
    Nakashima M. Induction of dentin formation on canine amputated pulp by recombinant human bone morphogenetic proteins (BMP)-2 and -4. J Dent Res. 1994;73(9):1515–22.PubMedGoogle Scholar
  70. 70.
    Nakashima M. Induction of dentine in amputated pulp of dogs by recombinant human bone morphogenetic proteins-2 and -4 with collagen matrix. Arch Oral Biol. 1994;39(12):1085–9.PubMedCrossRefGoogle Scholar
  71. 71.
    Rutherford RB, Gu K. Treatment of inflamed ferret dental pulps with recombinant bone morphogenetic protein-7. Eur J Oral Sci. 2000;108(3):202–6.PubMedCrossRefGoogle Scholar
  72. 72.
    Jiang N, Zhou J, Chen M, Schiff MD, Lee CH, Kong K, et al. Postnatal epithelium and mesenchyme stem/progenitor cells in bioengineered amelogenesis and dentinogenesis. Biomaterials. 2014;35(7):2172–80.PubMedCrossRefGoogle Scholar
  73. 73.
    Lin ZM, Qin W, Zhang NH, Xiao L, Ling JQ. Adenovirus-mediated recombinant human bone morphogenetic protein-7 expression promotes differentiation of human dental pulp cells. J Endod. 2007;33(8):930–5.PubMedCrossRefGoogle Scholar
  74. 74.
    Massague J. Receptors for the TGF-beta family. Cell. 1992;69(7):1067–70.PubMedCrossRefGoogle Scholar
  75. 75.
    Liu J, Jin T, Chang S, Ritchie HH, Smith AJ, Clarkson BH. Matrix and TGF-beta-related gene expression during human dental pulp stem cell (DPSC) mineralization. Vitro Cell Dev Biol Anim. 2007;43(3–4):120–8.CrossRefGoogle Scholar
  76. 76.
    Nakatake Y, Hoshikawa M, Asaki T, Kassai Y, Itoh N. Identification of a novel fibroblast growth factor, FGF-22, preferentially expressed in the inner root sheath of the hair follicle. Biochim Biophys Acta. 2001;1517(3):460–3.PubMedCrossRefGoogle Scholar
  77. 77.
    Nishimura T, Nakatake Y, Konishi M, Itoh N. Identification of a novel FGF, FGF-21, preferentially expressed in the liver. Biochim Biophys Acta. 2000;1492(1):203–6.PubMedCrossRefGoogle Scholar
  78. 78.
    Powers CJ, McLeskey SW, Wellstein A. Fibroblast growth factors, their receptors and signaling. Endocr Relat Cancer. 2000;7(3):165–97.PubMedCrossRefGoogle Scholar
  79. 79.
    Yamashita T, Yoshioka M, Itoh N. Identification of a novel fibroblast growth factor, FGF-23, preferentially expressed in the ventrolateral thalamic nucleus of the brain. Biochem Biophys Res Commun. 2000;277(2):494–8.PubMedCrossRefGoogle Scholar
  80. 80.
    Osathanon T, Nowwarote N, Pavasant P. Basic fibroblast growth factor inhibits mineralization but induces neuronal differentiation by human dental pulp stem cells through a FGFR and PLC gamma signaling pathway. J Cell Biochem. 2011;112(7):1807–16.PubMedCrossRefGoogle Scholar
  81. 81.
    Wu J, Huang GT, He W, Wang P, Tong Z, Jia Q, et al. Basic fibroblast growth factor enhances stemness of human stem cells from the apical papilla. J Endod. 2012;38(5):614–22.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Shimabukuro Y, Ueda M, Ozasa M, Anzai J, Takedachi M, Yanagita M, et al. Fibroblast growth factor-2 regulates the cell function of human dental pulp cells. J Endod. 2009;35(11):1529–35.PubMedCrossRefGoogle Scholar
  83. 83.
    He H, Yu J, Liu Y, Lu S, Liu H, Shi J, et al. Effects of FGF2 and TGFbeta1 on the differentiation of human dental pulp stem cells in vitro. Cell Biol Int. 2008;32(7):827–34.PubMedCrossRefGoogle Scholar
  84. 84.
    Kim J, Park JC, Kim SH, Im GI, Kim BS, Lee JB, et al. Treatment of FGF-2 on stem cells from inflamed dental pulp tissue from human deciduous teeth. Oral Dis. 2014;20(2):191–204.PubMedCrossRefGoogle Scholar
  85. 85.
    Grando Mattuella L, Westphalen Bento L, de Figueiredo JA, Nor JE, de Araujo FB, Fossati AC. Vascular endothelial growth factor and its relationship with the dental pulp. J Endod. 2007;33(5):524–30.PubMedCrossRefGoogle Scholar
  86. 86.
    Marchionni C, Bonsi L, Alviano F, Lanzoni G, Di Tullio A, Costa R, et al. Angiogenic potential of human dental pulp stromal (stem) cells. Int J Immunopathol Pharmacol. 2009;22(3):699–706.PubMedGoogle Scholar
  87. 87.
    Demarco FF, Conde MC, Cavalcanti BN, Casagrande L, Sakai VT, Nor JE. Dental pulp tissue engineering. Braz Dent J. 2011;22(1):3–13.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Magnucki G, Schenk U, Ahrens S, Navarrete Santos A, Gernhardt CR, Schaller HG, et al. Expression of the IGF-1, IGFBP-3 and IGF-1 receptors in dental pulp stem cells and impacted third molars. J Oral Sci. 2013;55(4):319–27.PubMedCrossRefGoogle Scholar
  89. 89.
    Denholm IA, Moule AJ, Bartold PM. The behaviour and proliferation of human dental pulp cell strains in vitro, and their response to the application of platelet-derived growth factor-BB and insulin-like growth factor-1. Int Endod J. 1998;31(4):251–8.PubMedCrossRefGoogle Scholar
  90. 90.
    Yu Y, Mu J, Fan Z, Lei G, Yan M, Wang S, et al. Insulin-like growth factor 1 enhances the proliferation and osteogenic differentiation of human periodontal ligament stem cells via ERK and JNK MAPK pathways. Histochem Cell Biol. 2012;137(4):513–25.PubMedCrossRefGoogle Scholar
  91. 91.
    Feng X, Huang D, Lu X, Feng G, Xing J, Lu J, et al. Insulin-like growth factor 1 can promote proliferation and osteogenic differentiation of human dental pulp stem cells via mTOR pathway. Dev Growth Differ. 2014.Google Scholar
  92. 92.
    Leong WK, Henshall TL, Arthur A, Kremer KL, Lewis MD, Helps SC, et al. Human adult dental pulp stem cells enhance poststroke functional recovery through non-neural replacement mechanisms. Stem Cells Transl Med. 2012;1(3):177–87.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Mead B, Logan A, Berry M, Leadbeater W, Scheven BA. Intravitreally transplanted dental pulp stem cells promote neuroprotection and axon regeneration of retinal ganglion cells after optic nerve injury. Invest Ophthalmol Vis Sci. 2013;54(12):7544–56.PubMedCrossRefGoogle Scholar
  94. 94.
    Esmaeili A, Alifarja S, Nourbakhsh N, Talebi A. Messenger RNA expression patterns of neurotrophins during transdifferentiation of stem cells from human-exfoliated deciduous teeth into neural-like cells. Avicenna J Med Biotechnol. 2014;6(1):21–6.PubMedPubMedCentralGoogle Scholar
  95. 95.
    Artavanis-Tsakonas S, Muskavitch MA. Notch: the past, the present, and the future. Curr Top Dev Biol. 2010;92:1–29.Google Scholar
  96. 96.
    He F, Yang Z, Tan Y, Yu N, Wang X, Yao N, et al. Effects of Notch ligand Delta1 on the proliferation and differentiation of human dental pulp stem cells in vitro. Arch Oral Biol. 2009;54(3):216–22.PubMedCrossRefGoogle Scholar
  97. 97.
    Zhang C, Chang J, Sonoyama W, Shi S, Wang CY. Inhibition of human dental pulp stem cell differentiation by Notch signaling. J Dent Res. 2008;87(3):250–5.PubMedCrossRefGoogle Scholar
  98. 98.
    Johnson GL, Lapadat R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science. 2002;298(5600):1911–2.PubMedCrossRefGoogle Scholar
  99. 99.
    Williams DW, Wu H, Oh JE, Fakhar C, Kang MK, Shin KH, et al. 2-Hydroxyethyl methacrylate inhibits migration of dental pulp stem cells. J Endod. 2013;39(9):1156–60.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Vandomme J, Touil Y, Ostyn P, Olejnik C, Flamenco P, El Machhour R, et al. Insulin-like growth factor 1 receptor and p38 mitogen-activated protein kinase signals inversely regulate signal transducer and activator of transcription 3 activity to control human dental pulp stem cell quiescence, propagation, and differentiation. Stem Cells Devel. 2014;23(8):839–51.CrossRefGoogle Scholar
  101. 101.
    Hata M, Naruse K, Ozawa S, Kobayashi Y, Nakamura N, Kojima N, et al. Mechanical stretch increases the proliferation while inhibiting the osteogenic differentiation in dental pulp stem cells. Tissue Eng Part A. 2013;19(5–6):625–33.PubMedCrossRefGoogle Scholar
  102. 102.
    Zhang H, Liu S, Zhou Y, Tan J, Che H, Ning F, et al. Natural mineralized scaffolds promote the dentinogenic potential of dental pulp stem cells via the mitogen-activated protein kinase signaling pathway. Tissue Eng Part A. 2012;18(7–8):677–91.PubMedCrossRefGoogle Scholar
  103. 103.
    Boyce BF, Yamashita T, Yao Z, Zhang Q, Li F, Xing L. Roles for NF-kappaB and c-Fos in osteoclasts. J Bone Miner Metab 2005;23 Suppl:11–15.Google Scholar
  104. 104.
    Paula-Silva FW, Ghosh A, Silva LA, Kapila YL. TNF-alpha promotes an odontoblastic phenotype in dental pulp cells. J Dent Res. 2009;88(4):339–44.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Wang Y, Zheng Y, Wang Z, Li J, Zhang G, Yu J. 10(-7) m 17beta-oestradiol enhances odonto/osteogenic potency of human dental pulp stem cells by activation of the NF-kappaB pathway. Cell Prolif. 2013;46(6):677–84.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Wang Y, Yan M, Wang Z, Wu J, Zheng Y, Yu J. Dental pulp stem cells from traumatically exposed pulps exhibited an enhanced osteogenic potential and weakened odontogenic capacity. Arch Oral Biol. 2013;58(11):1709–17.PubMedCrossRefGoogle Scholar
  107. 107.
    Tai TF, Chan CP, Lin CC, Chen LI, Jeng JH, Chang MC. Transforming growth factor beta2 regulates growth and differentiation of pulp cells via ALK5/Smad2/3. J Endod. 2008;34(4):427–32.PubMedCrossRefGoogle Scholar
  108. 108.
    Yongchaitrakul T, Pavasant P. Transforming growth factor-beta 1 up-regulates the expression of nerve growth factor through mitogen-activated protein kinase signaling pathways in dental pulp cells. Eur J Oral Sci. 2007;115(1):57–63.PubMedCrossRefGoogle Scholar
  109. 109.
    Oka S, Oka K, Xu X, Sasaki T, Bringas P Jr, Chai Y. Cell autonomous requirement for TGF-beta signaling during odontoblast differentiation and dentin matrix formation. Mech Dev. 2007;124(6):409–15.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Scheller EL, Chang J, Wang CY. Wnt/beta-catenin inhibits dental pulp stem cell differentiation. J Dent Res. 2008;87(2):126–30.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Zhang J, Park YD, Bae WJ, El-Fiqi A, Shin SH, Lee EJ, et al. Effects of bioactive cements incorporating zinc-bioglass nanoparticles on odontogenic and angiogenic potential of human dental pulp cells. J Biomater Appl. 2014.Google Scholar
  112. 112.
    Smith A, Robinson V, Patel K, Wilkinson DG. The EphA4 and EphB1 receptor tyrosine kinases and ephrin-B2 ligand regulate targeted migration of branchial neural crest cells. Curr Biol. 1997;7(8):561–70.PubMedCrossRefGoogle Scholar
  113. 113.
    Stokowski A, Shi S, Sun T, Bartold PM, Koblar SA, Gronthos S. EphB/ephrin-B interaction mediates adult stem cell attachment, spreading, and migration: implications for dental tissue repair. Stem Cells. 2007;25(1):156–64.PubMedCrossRefGoogle Scholar
  114. 114.
    Liu L, Ling J, Wei X, Wu L, Xiao Y. Stem cell regulatory gene expression in human adult dental pulp and periodontal ligament cells undergoing odontogenic/osteogenic differentiation. J Endod. 2009;35(10):1368–76.PubMedCrossRefGoogle Scholar
  115. 115.
    Tada H, Nemoto E, Foster BL, Somerman MJ, Shimauchi H. Phosphate increases bone morphogenetic protein-2 expression through cAMP-dependent protein kinase and ERK1/2 pathways in human dental pulp cells. Bone. 2011;48(6):1409–16.PubMedCrossRefGoogle Scholar
  116. 116.
    Lin PS, Chang MC, Chan CP, Lee SY, Lee JJ, Tsai YL, et al. Transforming growth factor beta1 down-regulates Runx-2 and alkaline phosphatase activity of human dental pulp cells via ALK5/Smad2/3 signaling. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;111(3):394–400.PubMedCrossRefGoogle Scholar
  117. 117.
    Wang FM, Hu T, Zhou X. p38 mitogen-activated protein kinase and alkaline phosphatase in human dental pulp cells. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;102(1):114–8.PubMedCrossRefGoogle Scholar
  118. 118.
    Pantovic A, Krstic A, Janjetovic K, Kocic J, Harhaji-Trajkovic L, Bugarski D, et al. Coordinated time-dependent modulation of AMPK/Akt/mTOR signaling and autophagy controls osteogenic differentiation of human mesenchymal stem cells. Bone. 2013;52(1):524–31.PubMedCrossRefGoogle Scholar
  119. 119.
    He WX, Wang ZH, Zhou ZY, Zhang YQ, Zhu QL, Wei KW, et al. Lipopolysaccharide Enhances Wnt5a expression through toll-like receptor 4, myeloid differentiating factor 88, Phosphatidylinositol 3-OH Kinase/AKT and nuclear factor kappa B pathways in human dental pulp stem cells. J Endod. 2014;40(1):69–75.PubMedCrossRefGoogle Scholar
  120. 120.
    Solozobova V, Wyvekens N, Pruszak J. Lessons from the embryonic neural stem cell niche for neural lineage differentiation of pluripotent stem cells. Stem cell Rev. 2012;8(3):813–29.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Nair R, Ngangan AV, Kemp ML, McDevitt TC. Gene expression signatures of extracellular matrix and growth factors during embryonic stem cell differentiation. PLoS ONE. 2012;7(10):e42580.PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Dallas SL, Rosser JL, Mundy GR, Bonewald LF. Proteolysis of latent transforming growth factor-beta (TGF-beta)-binding protein-1 by osteoclasts. A cellular mechanism for release of TGF-beta from bone matrix. J Biol Chem. 2002;277(24):21352–60.PubMedCrossRefGoogle Scholar
  123. 123.
    Garcion E, Halilagic A, Faissner A, ffrench-Constant C. Generation of an environmental niche for neural stem cell development by the extracellular matrix molecule tenascin C. Development. 2004;131(14):3423–3432.Google Scholar
  124. 124.
    Jadlowiec JA, Zhang X, Li J, Campbell PG, Sfeir C. Extracellular matrix-mediated signaling by dentin phosphophoryn involves activation of the Smad pathway independent of bone morphogenetic protein. J Biol Chem. 2006;281(9):5341–7.PubMedCrossRefGoogle Scholar
  125. 125.
    Armstrong MT, Armstrong PB. Growth factor modulation of the extracellular matrix. Exp Cell Res. 2003;288(2):235–45.PubMedCrossRefGoogle Scholar
  126. 126.
    Vidane AS, Zomer HD, Oliveira BM, Guimaraes CF, Fernandes CB, Perecin F, et al. Reproductive stem cell differentiation: extracellular matrix, tissue microenvironment, and growth factors direct the mesenchymal stem cell lineage commitment. Reprod Sci. 2013;20(10):1137–43.PubMedCrossRefGoogle Scholar
  127. 127.
    Huang CH, Tseng WY, Yao CC, Jeng JH, Young TH, Chen YJ. Glucosamine promotes osteogenic differentiation of dental pulp stem cells through modulating the level of the transforming growth factor-beta type I receptor. J Cell Physiol. 2010;225(1):140–51.PubMedCrossRefGoogle Scholar
  128. 128.
    Mayo V, Sawatari Y, Huang CY, Garcia-Godoy F. Neural crest-derived dental stem cells–where we are and where we are going. J Dent. 2014;42(9):1043–51.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Jinhua Yu
    • 1
  • Mohamed Jamal
    • 2
  • Franklin Garcia-Godoy
    • 3
  • George T.-J. Huang
    • 3
  1. 1.Key Laboratory of Oral Diseases of Jiangsu Province, Institute of StomatologyNanjing Medical UniversityNanjingChina
  2. 2.Department of Endodontics, Henry M. Goldman School of Dental MedicineBoston UniversityBostonUSA
  3. 3.Department of Bioscience Research, College of DentistryUniversity of Tennessee Health Science CenterMemphisUSA

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