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Corneal Regeneration pp 145–154Cite as

One Cell, Two Phenotypes: Capturing Pluripotency for Corneal Regeneration

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Part of the book series: Essentials in Ophthalmology ((ESSENTIALS))

Abstract

A major goal for corneal restoration and regeneration over the last decade has been the production of bioengineered corneas in vitro for transplant, with many research laboratories investigating a variety of scaffold materials aimed at preserving the physiological and optical properties of the cornea. However, advances in cell reprogramming and in gene therapy have made the possibility of in vivo corneal engineering a distinct possibility. Here we describe the methods by which we have been able to induce in vivo keratocytes to produce proteins normally associated with other cell phenotypes, which may prove to be simple and effective examples of in vivo corneal engineering.

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References

  1. Chen Z, You J, Liu X, Cooper S, Hodge C, Sutton G, Crook JM, Wallace GG. Biomaterials for corneal bioengineering. Biomed Mater. Accepted Manuscript online 12 October 2017.

    Google Scholar 

  2. Sasamoto Y, Hayashi R, Park SJ, Saito-Adachi M, Suzuki Y, Kawasaki S, Quantock AJ, Nakai K, Tsujikawa M, Nishida K. PAX6 isoforms, along with reprogramming factors, differentially regulate the induction of cornea-specific genes. Sci Rep. 2016;6:20807.

    Article  CAS  Google Scholar 

  3. Amici AW, Onikoyi FO, Bonfanti P. Lineage potential, plasticity and environmental reprogramming of epithelial stem/progenitor cells. Biochem Soc Trans. 2014;42(3):637–44.

    Article  CAS  Google Scholar 

  4. Solinis MA, del Pozo-Rodriguez A, Apaolaza PS, Rodriguez-Gascon A. Treatment of ocular disorders by gene therapy. Eur J Pharm Biopharm. 2015;95(Pt B):331–42.

    Article  CAS  Google Scholar 

  5. Farjadnia M, Naderan M, Mohammadpour M. Gene therapy in keratoconus. Oman J Ophthalmol. 2015;8(1):3–8.

    Article  Google Scholar 

  6. Hendrix MJ, Hay ED, von der Mark K, Linsenmayer TF. Immunohistochemical localization of collagen types I and II in the developing chick cornea and tibia by electron microscopy. Invest Ophthalmol Vis Sci. 1982;22(3):359–75.

    Google Scholar 

  7. Toole BP. Transitions in extracellular macromolecules during avian ocular development. Prog Clin Biol Res. 1982;82:17–34.

    CAS  PubMed  Google Scholar 

  8. Marshall GE, Konstas AG, Lee WR. Immunogold fine structural localization of extracellular matrix components in aged human cornea. I. Types I-IV collagen and laminin. Graefes Arch Clin Exp Ophthalmol. 1991;229(2):157–63.

    Article  CAS  Google Scholar 

  9. Snyder MC, Bergmanson JP, Doughty MJ. Keratocytes: no more the quiet cells. J Am Optom Assoc. 1998;69(3):180–7.

    CAS  PubMed  Google Scholar 

  10. West-Mays JA, Dwivedi DJ. The keratocyte: corneal stromal cell with variable repair phenotypes. Int J Biochem Cell Biol. 2006;38(10):1625–31.

    Article  CAS  Google Scholar 

  11. Torricelli AA, Santhanam A, Wu J, Singh V, Wilson SE. The corneal fibrosis response to epithelial-stromal injury. Exp Eye Res. 2016;142:110–8.

    Article  CAS  Google Scholar 

  12. Ljubimov AV, Saghizadeh M. Progress in corneal wound healing. Prog Retin Eye Res. 2015;49:17–45.

    Article  CAS  Google Scholar 

  13. Cintron C, Hong BS, Covington HI, Macarak EJ. Heterogeneity of collagens in rabbit cornea: type III collagen. Invest Ophthalmol Vis Sci. 1988;29(5):767–75.

    CAS  PubMed  Google Scholar 

  14. Manificat H, Rovère MR, Galiacy SD, Malecaze F, Hulmes DJ, Moali C, Damour O. Development of ex vivo organ culture models to mimic human corneal scarring. Mol Vis. 2012;18:2896–908. Epub 2012 Dec 1.

    Google Scholar 

  15. Kaltschmidt B; Kaltschmidt C, Widera D. Adult craniofacial stem cells: sources and relation to the neural crest. Stem Cell Rev. 2012;8(3):658–71.

    Article  Google Scholar 

  16. Merrell AJ, Stanger BZ. Adult cell plasticity in vivo: de-differentiation and transdifferentiation are back in style. Nat Rev Mol Cell Biol. 2016;17(7):413–25.

    Article  CAS  Google Scholar 

  17. Hay ED, Zuk A. Transformations between epithelium and mesenchyme: normal, pathological, and experimentally induced. Am J Kidney Dis. 1995;26(4):678–90.

    Article  CAS  Google Scholar 

  18. Suzuki K, Yokoyama C, Higashi Y, Daikoku T, Mizoguchi S, Saika S, Wakayama YG. Symposium: epithelial-mesenchymal interaction regulates tissue formation and characteristics: insights for corneal development. Ocul Surf. 2012;10(4):217–20.

    Article  Google Scholar 

  19. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–76.

    Article  CAS  Google Scholar 

  20. Lin T, Wu S. Reprogramming with small molecules instead of exogenous transcription factors. Stem Cells Int. 2015;2015:794632.

    Article  Google Scholar 

  21. Greene CA, Chang C-Y, Fraser CJ, Nelidova DE, Chen JA, Lim A, Brebner A, McGhee J, Sherwin T, Green CR. Cells from the adult corneal stroma can be reprogrammed to a neuron-like cell using exogenous growth factors. Exp Cell Res. 2014;322(1):122–32.

    Article  CAS  Google Scholar 

  22. Greene CA, Green CR, Sherwin T. Transdifferentiation of chondrocytes into neuron-like cells induced by neuronal lineage specifying growth factors. Cell Biol Int. 2015;39(2):185–91.

    Article  CAS  Google Scholar 

  23. Quintana L, zur Nieden NI, Semino CE. Morphogenetic and regulatory mechanisms during developmental chondrogenesis: new paradigms for cartilage tissue engineering. Tissue Eng Part B Rev. 2009;15(1):29–41.

    Article  CAS  Google Scholar 

  24. Shah M, Foreman DM, Ferguson MW. Neutralisation of TGF-beta 1 and TGF-beta 2 or exogenous addition of TGF-beta 3 to cutaneous rat wounds reduces scarring. J Cell Sci. 1995;108(3):985–1002.

    CAS  PubMed  Google Scholar 

  25. Karamichos D, Hutcheon AEK, Zieske JD. Transforming growth factor-β3 regulates assembly of a non-fibrotic matrix in a 3D corneal model. J Tissue Eng Regen Med. 2011;5(8):e228.

    Article  CAS  Google Scholar 

  26. Wa Q, Gao M, Dai X, Yu T, Zhou Z, Xu D, Zou X. Induction of chondrogenic differentiation of mouse embryonic mesenchymal stem cells through an in vitro pellet model. Cell Biol Int. 2015;39(6):657–65.

    Article  CAS  Google Scholar 

  27. Greene CA, Green CR, Dickinson ME, Johnson V, Sherwin T. Keratocytes are induced to produce collagen type II: a new strategy for in vivo corneal matrix regeneration. Exp Cell Res. 2016;347:241–9.

    Article  CAS  Google Scholar 

  28. Kapadia K. Safety of a novel in vivo corneal tissue regeneration therapy for Keratoconus. Master of Science in Biomedical Science Thesis; 2017.

    Google Scholar 

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Compliance with Ethical Requirements

Carol Greene, Colin Green and Trevor Sherwin are coinventors listed on patent PCT/NZ2016/050033, application date: 05 Mar 2015. Kushant Kapadia has no conflict of interest to declare. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study. All institutional and national guidelines for the care and use of laboratory animals were followed.

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Authors and Affiliations

  1. Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand

    Trevor Sherwin, Carol Ann Greene, Colin R. Green & Kushant R. Kapadia

Authors
  1. Trevor Sherwin
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  2. Carol Ann Greene
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  3. Colin R. Green
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  4. Kushant R. Kapadia
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Corresponding author

Correspondence to Trevor Sherwin .

Editor information

Editors and Affiliations

  1. Miguel Hernández University , Alicante, Spain

    Jorge L. Alió

  2. Vissum-Instituto Oftalmologico de Alica, University Miguel Hernandez, Alicante, Alicante, Spain

    Jorge L. Alió del Barrio

  3. Vissum Corporation, Madrid, Spain

    Francisco Arnalich-Montiel

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Sherwin, T., Greene, C.A., Green, C.R., Kapadia, K.R. (2019). One Cell, Two Phenotypes: Capturing Pluripotency for Corneal Regeneration. In: Alió, J., Alió del Barrio, J., Arnalich-Montiel, F. (eds) Corneal Regeneration . Essentials in Ophthalmology. Springer, Cham. https://doi.org/10.1007/978-3-030-01304-2_10

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  • DOI: https://doi.org/10.1007/978-3-030-01304-2_10

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-01303-5

  • Online ISBN: 978-3-030-01304-2

  • eBook Packages: MedicineMedicine (R0)

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