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Induced Pluripotent Stem Cells Derived from Dental Stem Cells: A New Tool for Cellular Therapy

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Dental Stem Cells

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

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Abstract

Induced pluripotent stem cells (iPSCs) are a type of experimentally produced pluripotent stem cell (PSC), which share similar features with embryonic stem cells (ES) isolated directly from early embryos. Shinya Yamanaka’s lab in Kyoto, Japan was the first to develop iPSCs in 2006 by the introduction of four genes that encode transcription factors of PSC into mouse embryonic fibroblasts—a process known as “reprogramming”. Later on, different animal and human fetal or adult somatic cell types have been converted into iPSCs using this technology, demonstrating similarities and slight differences between iPSCs lines, which are known to depend on the origin of the cells used in reprogramming. The present chapter will provide an overview of iPSCs derived from dental stem cells (DSCs), such as stem cells isolated from apical papilla (SCAPs), stem cells from exfoliated deciduous teeth (SHEDS), from pulp of third molars and adult permanent teeth (DPSCs). We will discuss the origin of the cells used for reprogramming, factors which may favor or hinter the reprogramming process, methods and efficiency of cell reprogramming; the differentiation ability of iPSCs derived from DSCs; their safety, tolerance by the host and regenerative potential in preclinical models, as well as the use of these cells in toxicological studies, disease modeling and drug discovery. The possible use of iPSCs obtained from DSCs as a new tool for regenerative therapy will also be shortly discussed.

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References

  1. Boehnke K, Falkowska-Hansen B, Stark HJ, Boukamp P (2012) Stem cells of the human epidermis and their niche: composition and function in epidermal regeneration and carcinogenesis. Carcinogenesis 33(7):1247–1258

    Article  CAS  PubMed  Google Scholar 

  2. Mouret S, Forestier A, Douki T (2012) The specificity of UVA-induced DNA damage in human melanocytes. Photochem Photobiol Sci 11(1):155–162

    Article  CAS  PubMed  Google Scholar 

  3. Haase A, Olmer R, Schwanke K et al (2009) Generation of induced pluripotent stem cells from human cord blood. Cell Stem Cell 5(4):434–441

    Article  CAS  PubMed  Google Scholar 

  4. Achilleos A, Trainor PA (2012) Neural crest stem cells: discovery, properties and potential for therapy. Cell Res 22(2):288–304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kerkis I, Kerkis A, Dozortsev D et al (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):105–116

    Article  CAS  PubMed  Google Scholar 

  6. Kerkis I, Caplan AI (2012) Stem cells in dental pulp of deciduous teeth. Tissue Eng Part B Rev 18(2):129–138

    Article  CAS  PubMed  Google Scholar 

  7. Kerkis I, Kerkis A, Lizier NF, Wenceslau CV (2015) Dental stem cells: risk and responsibilities. In: Bhattacharya N, Stubblefield FG (eds) Regenerative medicine using non-fetal sources of stem cells. Springer, London, pp 171–175

    Google Scholar 

  8. Lizier NF, Kerkis I, Wenceslau CV (2013) Generation of induced pluripotent stem cells from dental pulp somatic cells, pluripotent stem cells. In: Bhartiya D (ed) Pluripotent stem cells. inTech, Rijeka. doi:10.5772/55856

    Google Scholar 

  9. Shakhova O, Sommer L (2008) Neural crest-derived stem cells. In: Gage F, Watt F (eds) StemBook. The Stem Cell Research Community, Boston, http://www.ncbi.nlm.nih.gov/books/NBK44752/

  10. Liu J, Yu F, Sun Y et al (2015) Concise reviews: characteristics and potential applications of human dental tissue-derived mesenchymal stem cells. Stem Cells 33(3):627–638

    Google Scholar 

  11. Ponnaiyan D (2014) Do dental stem cells depict distinct characteristics? - Establishing their “phenotypic fingerprint”. Dent Res J (Isfahan) 11(2):163–172

    Google Scholar 

  12. Park JC, Kim JM, Jung IH et al (2011) Isolation and characterization of human periodontal ligament (PDL) stem cells (PDLSCs) from the inflamed PDL tissue: in vitro and in vivo evaluations. J Clin Periodontol 38(8):721–731

    Article  PubMed  Google Scholar 

  13. Zhang J, An Y, Gao LN, Zhang YJ, Jin Y, Chen FM (2012) The effect of aging on the pluripotential capacity and regenerative potential of human periodontal ligament stem cells. Biomaterials 33(29):6974–6986

    Article  CAS  PubMed  Google Scholar 

  14. Beltrao-Braga PC, Pignatari GC, Maiorka PC et al (2011) Feeder-free derivation of induced pluripotent stem cells from human immature dental pulp stem cells. Cell Transplant 20(11–12):1707–1719

    Article  PubMed  Google Scholar 

  15. Chang YC, Li WC, Twu NF et al (2014) Induction of dental pulp-derived induced pluripotent stem cells in the absence of c-Myc for differentiation into neuron-like cells. J Chin Med Assoc 77(12):618–625

    Article  PubMed  Google Scholar 

  16. Dambrot C, van de Pas S, van Zijl L et al (2013) Polycistronic lentivirus induced pluripotent stem cells from skin biopsies after long term storage, blood outgrowth endothelial cells and cells from milk teeth. Differentiation 85(3):101–109

    Article  CAS  PubMed  Google Scholar 

  17. Iida K, Takeda-Kawaguchi T, Hada M et al (2013) Hypoxia-enhanced derivation of iPSCs from human dental pulp cells. J Dent Res 92(10):905–910

    Article  CAS  PubMed  Google Scholar 

  18. Oda Y, Yoshimura Y, Ohnishi H et al (2010) Induction of pluripotent stem cells from human third molar mesenchymal stromal cells. J Biol Chem 285(38):29270–29278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Takeda-Kawaguchi T, Sugiyama K, Chikusa S et al (2014) Derivation of iPSCs after culture of human dental pulp cells under defined conditions. PLoS One 9(12):e115392. doi:10.1371/journal.pone.0115392

    Article  PubMed  PubMed Central  Google Scholar 

  20. Tamaoki N, Takahashi K, Aoki H et al (2014) The homeobox gene DLX4 promotes generation of human induced pluripotent stem cells. Sci Rep 4:7283. doi:10.1038/srep07283

    Article  PubMed  PubMed Central  Google Scholar 

  21. Tamaoki N, Takahashi K, Tanaka T et al (2010) Dental pulp cells for induced pluripotent stem cell banking. J Dent Res 89(8):773–778

    Article  CAS  PubMed  Google Scholar 

  22. Yan X, Qin H, Qu C, Tuan RS, Shi S, Huang GT (2010) iPS cells reprogrammed from human mesenchymal-like stem/progenitor cells of dental tissue origin. Stem Cells Dev 19(4):469–480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Yoo CH, Na HJ, Lee DS et al (2013) Endothelial progenitor cells from human dental pulp-derived iPS cells as a therapeutic target for ischemic vascular diseases. Biomaterials 34(33):8149–8160

    Article  CAS  PubMed  Google Scholar 

  24. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676

    Article  CAS  PubMed  Google Scholar 

  25. da Cunha JM, da Costa-Neves A, Kerkis I, da Silva MC (2013) Pluripotent stem cell transcription factors during human odontogenesis. Cell Tissue Res 353(3):435–441

    Article  PubMed  Google Scholar 

  26. Tompkins K (2006) Molecular mechanisms of cytodifferentiation in mammalian tooth development. Connective tissue research 47(3):111–118

    Article  CAS  PubMed  Google Scholar 

  27. Lizier NF, Kerkis A, Gomes CM et al (2012) Scaling-up of dental pulp stem cells isolated from multiple niches. Plos One 7(6):e39885. doi:10.1371/journal.pone.0039885

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Dominici M, Le Blanc K, Mueller I et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4):315–317

    Article  CAS  PubMed  Google Scholar 

  29. Warlich E, Kuehle J, Cantz T et al (2011) Lentiviral vector design and imaging approaches to visualize the early stages of cellular reprogramming. Mol Ther 19(4):782–789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Fusaki N, Ban H, Nishiyama A, Saeki K, Hasegawa M (2009) Efficient induction of transgene-free human pluripotent stem cells using a vector based on Sendai virus, an RNA virus that does not integrate into the host genome. Proc Jpn Acad Ser B Phys Biol Sci 85(8):348–362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Yoshida Y, Takahashi K, Okita K, Ichisaka T, Yamanaka S (2009) Hypoxia enhances the generation of induced pluripotent stem cells. Cell Stem Cell 5(3):237–241

    Article  CAS  PubMed  Google Scholar 

  32. Muchkaeva IA, Dashinimaev EB, Terskikh VV, Sukhanov YV, Vasiliev AV (2012) Molecular mechanisms of induced pluripotency. Acta Naturae 4(1):12–22

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Patel M, Yang S (2010) Advances in reprogramming somatic cells to induced pluripotent stem cells. Stem Cell Rev 6(3):367–680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Zouboulis CC, Adjaye J, Akamatsu H, Moe-Behrens G, Niemann C (2008) Human skin stem cells and the ageing process. Exp Gerontol 43(11):986–997

    Article  CAS  PubMed  Google Scholar 

  35. Banito A, Rashid ST, Acosta JC et al (2009) Senescence impairs successful reprogramming to pluripotent stem cells. Genes Dev 23(18):2134–2139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Nolte C, Krumlauf R (2000) Expression of Hox genes in the nervous system of vertebrates. Madame Curie Bioscience Database [Internet]. Landes Bioscience, Austin (TX)

    Google Scholar 

  37. Larsen KB, Lutterodt MC, Mollgard K, Moller M (2010) Expression of the homeobox genes OTX2 and OTX1 in the early developing human brain. J Histochem Cytochem 58(7):669–678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Salvatierra J, Lee DA, Zibetti C et al (2014) The LIM homeodomain factor Lhx2 is required for hypothalamic tanycyte specification and differentiation. J Neurosci 34(50):16809–16820

    Article  PubMed  PubMed Central  Google Scholar 

  39. Vargha-Khadem F, Gadian DG, Copp A, Mishkin M (2005) FOXP2 and the neuroanatomy of speech and language. Nat Rev Neurosci 6(2):131–138

    Article  CAS  PubMed  Google Scholar 

  40. Zembrzycki A, Perez-Garcia CG, Wang CF, Chou SJ, O’Leary DD (2015) Postmitotic regulation of sensory area patterning in the mammalian neocortex by Lhx2. Proc Natl Acad Sci U S A 112(21):6736–6741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Zhang YF, Liu LX, Cao HT et al (2015) Otx1 promotes basal dendritic growth and regulates intrinsic electrophysiological and synaptic properties of layer V pyramidal neurons in mouse motor cortex. Neuroscience 285:139–154

    Article  CAS  PubMed  Google Scholar 

  42. Chen J, Lin M, Foxe JJ et al (2013) Transcriptome comparison of human neurons generated using induced pluripotent stem cells derived from dental pulp and skin fibroblasts. PLoS One 8(10):e75682. doi:10.1371/journal.pone.0075682

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kume T (2010) Specification of arterial, venous, and lymphatic endothelial cells during embryonic development. Histol Histopathol 25(5):637–646

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Phillips W, Michell A, Pruess H, Barker RA (2009) Animal models of neurodegenerative diseases. Methods Mol Biol 549:137–155

    Article  CAS  PubMed  Google Scholar 

  45. Young AB (2009) Four decades of neurodegenerative disease research: how far we have come! J Neurosci 29(41):12722–12728

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Park IH, Arora N, Huo H et al (2008) Disease-specific induced pluripotent stem cells. Cell 134(5):877–886

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Soldner F, Hockemeyer D, Beard C et al (2009) Parkinson’s disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell 136(5):964–977

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Yagi T, Ito D, Okada Y et al (2011) Modeling familial Alzheimer’s disease with induced pluripotent stem cells. Hum Mol Genet 20(23):4530–4539

    Article  CAS  PubMed  Google Scholar 

  49. Zheng GP, Ge MH, Shu Q, Rojas M, Xu J (2013) Mesenchymal stem cells in the treatment of pediatric diseases. World J Pediatr 9(3):197–211

    Article  CAS  PubMed  Google Scholar 

  50. Hu BY, Weick JP, Yu J et al (2010) Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency. Proc Natl Acad Sci U S A 107(9):4335–4340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Osafune K, Caron L, Borowiak M et al (2008) Marked differences in differentiation propensity among human embryonic stem cell lines. Nat Biotechnol 26(3):313–315

    Article  CAS  PubMed  Google Scholar 

  52. Griesi-Oliveira K, Acab A, Gupta AR et al (2014) Modeling non-syndromic autism and the impact of TRPC6 disruption in human neurons. Mol Psychiatry. doi:10.1038/mp.2014.141

    PubMed  PubMed Central  Google Scholar 

  53. Li Y, Jia YC, Cui K et al (2005) Essential role of TRPC channels in the guidance of nerve growth cones by brain-derived neurotrophic factor. Nature 434(7035):894–898

    Article  CAS  PubMed  Google Scholar 

  54. Zhou J, Du W, Zhou K et al (2008) Critical role of TRPC6 channels in the formation of excitatory synapses. Nat Neurosci 11(7):741–743

    Article  CAS  PubMed  Google Scholar 

  55. Altshuler D, Daly MJ, Lander ES (2008) Genetic mapping in human disease. Science 322(5903):881–888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Tabar V, Studer L (2014) Pluripotent stem cells in regenerative medicine: challenges and recent progress. Nat Rev Genet 15(2):82–92

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Kim K, Doi A, Wen B, Ng K, Zhao R, Cahan P et al (2010) Epigenetic memory in induced pluripotent stem cells. Nature 467(7313):285–290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Polo JM, Liu S, Figueroa ME, Kulalert W, Eminli S, Tan KY et al (2010) Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells. Nat Biotechnol 28(8):848–855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Kuijk EW, Chuva de Sousa Lopes SM, Geijsen N, Macklon N, Roelen BA (2011) The different shades of mammalian pluripotent stem cells. Hum Reprod Update 17(2):254–271

    Google Scholar 

  60. Estrela C, Alencar AH, Kitten GT, Vencio EF, Gava E (2011) Mesenchymal stem cells in the dental tissues: perspectives for tissue regeneration. Braz Dent J 22(2):91–98

    PubMed  Google Scholar 

  61. Machado E, Fernandes MH, Gomes Pde S (2012) Dental stem cells for craniofacial tissue engineering. Oral Surg Oral Med Oral Pathol Oral Radiol 113(6):728–733

    Article  PubMed  Google Scholar 

  62. Wen Y, Wang F, Zhang W et al (2012) Application of induced pluripotent stem cells in generation of a tissue-engineered tooth-like structure. Tissue Eng Part A 18(15–16):1677–1685

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Laboratory of Genetics, Butantan Institute, Av. Vital Brasil 1500, São Paulo, CEP 05503-900, Brazil

    Irina Kerkis, Cristiane V. Wenceslau & Celine Pompeia

Authors
  1. Irina Kerkis
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  2. Cristiane V. Wenceslau
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  3. Celine Pompeia
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Corresponding author

Correspondence to Irina Kerkis .

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Editors and Affiliations

  1. Yeditepe University, Genetics and Bioengineering Department, Istanbul, Turkey

    Fikrettin Şahin

  2. Yeditepe University, Genetics and Bioengineering Department, Istanbul, Turkey

    Ayşegül Doğan

  3. Yeditepe University, Genetics and Bioengineering Department, ISTANBUL, Turkey

    Selami Demirci

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Kerkis, I., Wenceslau, C.V., Pompeia, C. (2016). Induced Pluripotent Stem Cells Derived from Dental Stem Cells: A New Tool for Cellular Therapy. In: Şahin, F., Doğan, A., Demirci, S. (eds) Dental Stem Cells. Stem Cell Biology and Regenerative Medicine. Springer, Cham. https://doi.org/10.1007/978-3-319-28947-2_7

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