Skip to main content
SpringerLink
Log in

Cell-based Therapy Using Induced Plutipotent Stem Cell

  • Chapter
  • First Online:
Corneal Regeneration

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

Abstract

Advanced cell-based therapy has seen important advances over the last decade. An emerging alternative source of cells for the treatment of ocular disease is adult tissue progenitor cells. Despite certain limitations about complete terminal differentiation, they benefit from high proliferative potential, lower immunogenicity, and being easy to obtain by minimally invasive techniques. Induced pluripotent stem cells (IPSCs) are an additional alternative that have unlimited translational potential in organ and tissue regeneration. From the first investigations into cell reprogramming, which induced a full state of cellular pluripotency, to the most recent approaches for direct reprogramming through non-integrative methodology, advances in the understanding of events related to cellular proliferation and differentiation for clinical purposes has improved considerably. Several research groups are working on innovative methods and techniques to obtain different cellular types of ocular tissue, including epithelial and endothelial cells of the cornea, neurosensory retina, and pigmentary epithelium, using cell differentiation from IPSC lines or cells in partial states of induced pluripotency. However, the large-scale application of IPSC lines is not yet possible because drawbacks related to their clinical applicability need to be resolved, such as the tolerability and safety of receptor tissue and the need to develop refined clinical grade protocols for their production and differentiation. This chapter is intended to present some of the main innovations and future perspectives concerning the clinical applicability of IPSCs in ocular pathology, focusing on the ocular surface pathology.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Osei-Bempong C, Figueiredo FC, Lako M. The limbal epithelium of the eye–a review of limbal stem cell biology, disease and treatment. BioEssays. 2013;35:211–9.

    Article  CAS  PubMed  Google Scholar 

  2. Casaroli-Marano RP, Nieto-Nicolau N, Martinez-Conesa EM. Progenitor cells for ocular surface regenerative therapy. Ophthalmic Res. 2013;49:115–21.

    Article  PubMed  Google Scholar 

  3. Utheim TP. Limbal epithelial cell therapy: past, present, and future. Methods Mol Biol. 2013;1014:3–43.

    Article  CAS  PubMed  Google Scholar 

  4. Pellegrini G, Rama P, Di Rocco A, Panaras A, De Luca M. Concise review: hurdles in a successful example of limbal stem cell-based regenerative medicine. Stem Cells. 2014;32:26–34.

    Article  PubMed  Google Scholar 

  5. Rama P, Ferrari G, Pellegrini G. Cultivated limbal epithelial transplantation. Curr Opin Ophthalmol. 2017;28:387–9.

    Article  PubMed  Google Scholar 

  6. Fuest M, Yam GH-F, Peh GS-L, Mehta JS. Advances in corneal cell therapy. Regen Med. 2016;11:601–15.

    Article  CAS  PubMed  Google Scholar 

  7. Kim K, Mian S. Diagnosis of corneal limbal stem cell deficiency. Curr Opin Ophthalmol. 2017;24:355–62.

    Article  Google Scholar 

  8. Casaroli-Marano R, Nieto-Nicolau N, Martínez-Conesa E, Edel M, Álvarez-Palomo AB. Potential role of induced pluripotent stem cells (IPSCs) for cell-based therapy of the ocular surface. J Clin Med. 2015;4:318–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Dua HS, Shanmuganathan VA, Powell-Richards AO, Tighe PJ, Joseph A. Limbal epithelial crypts: a novel anatomical structure and a putative limbal stem cell niche. Br J Ophthalmol. 2005;89:529–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gonzalez G, Sasamoto Y, Ksander BR, Frank MH, Frank NY. Limbal stem cells: identity, developmental origin, and therapeutic potential. Wiley Interdiscip Rev Dev Biol. 2017. https://doi.org/10.1002/wdev.303.

    Article  Google Scholar 

  11. Yeung AMH, Schlötzer-Schrehardt U, Kulkarni B, Tint NL, Hopkinson A, Dua HS. Limbal epithelial crypt: a model for corneal epithelial maintenance and novel limbal regional variations. Arch Ophthalmol. 2008;126:665–9.

    Article  PubMed  Google Scholar 

  12. Pellegrini G, Golisano O, Paterna P, Lambiase A, Bonini S, Rama P, et al. Location and clonal analysis of stem cells and their differentiated progeny in the human ocular surface. J Cell Biol. 1999;145:769–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Thoft RA, Friend J. The X, Y, Z hypothesis of corneal epithelial maintenance. Invest Ophthalmol Vis Sci. 1983;24:1442–3.

    CAS  PubMed  Google Scholar 

  14. Dua HS, Miri A, Alomar T, Yeung AM, Said DG. The role of limbal stem cells in corneal epithelial maintenance. Testing the dogma. Ophthalmology. 2009;116:856–63.

    Article  PubMed  Google Scholar 

  15. Yazdanpanah G, Jabbehdari S, Djalilian AR. Limbal and corneal epithelial homeostasis. Curr Opin Ophthalmol. 2017;28:348–54.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Majo F, Rochat A, Nicolas M, Jaoudé GA, Barrandon Y. Oligopotent stem cells are distributed throughout the mammalian ocular surface. Nature. 2008;456:250–4.

    Article  CAS  PubMed  Google Scholar 

  17. Zhang Y, Sun H, Liu Y, Chen S, Cai S, Zhu Y, et al. The limbal epithelial progenitors in the limbal niche environment. Int J Med Sci. 2016;13:835–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Pellegrini G, Rama P, Matuska S, Lambiase A, Bonini S, Pocobelli A, et al. Biological parameters determining the clinical outcome of autologous cultures of limbal stem cells. Regen Med. 2013;8:553–67.

    Article  CAS  PubMed  Google Scholar 

  19. Rama P, Matuska S, Paganoni G, Spinelli A, De Luca M, Pellegrini G. Limbal stem-cell therapy and long-term corneal regeneration. N Engl J Med. 2010;363:147–55.

    Article  CAS  PubMed  Google Scholar 

  20. Nieto-Nicolau N, Martínez-Conesa E, Casaroli-Marano R. Limbal stem cells from aged donors are a suitable source for clinical application. Stem Cells Int. 2016;2016:3032128.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Joe AW, Yeung SN. Concise review: identifying limbal stem cells: classical concepts and new challenges. Stem Cells Transl Med. 2014;3:318–22.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Huang M, Wang B, Wan P, Liang X, Wang X, Liu Y, et al. Roles of limbal microvascular net and limbal stroma in regulating maintenance of limbal epithelial stem cells. Cell Tissue Res. 2015;359:547–63.

    Article  CAS  PubMed  Google Scholar 

  24. Polisetti N, Zenkel M, Menzel-Severing J, Kruse FE, Schlötzer-Schrehardt U. Cell adhesion molecules and stem cell-niche-interactions in the limbal stem cell niche. Stem Cells. 2016;34:203–19.

    Article  CAS  PubMed  Google Scholar 

  25. Mali P, Yang L, Esvelt KM, Aach J, Guell M, DiCarlo JE, et al. RNA-guided human genome engineering via Cas9. Science. 2013;339:823–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Cabral T, DiCarlo JE, Justus S, Sengillo JD, Xu Y, Tsang SH. CRISPR applications in ophthalmologic genome surgery. Curr Opin Ophthalmol. 2017;28:252–9.

    Article  PubMed  PubMed Central  Google Scholar 

  27. 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  PubMed  Google Scholar 

  28. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318:1917–20.

    Article  CAS  PubMed  Google Scholar 

  29. Yamanaka S. Induced pluripotent stem cells: past, present, and future. Cell Stem Cell. 2012;10:678–84.

    Article  CAS  PubMed  Google Scholar 

  30. Compagnucci C, Bertini E. The potential of iPSCs for the treatment of premature aging disorders. Int J Mol Sci. 2017;18. https://doi.org/10.3390/ijms18112350.

  31. Li L, Chao J, Shi Y. Modeling neurological diseases using iPSC-derived neural cells: iPSC modeling of neurological diseases. Cell Tissue Res. 2018;371:143–51.

    Article  CAS  PubMed  Google Scholar 

  32. Grskovic M, Javaherian A, Strulovici B, Daley GQ. Induced pluripotent stem cells--opportunities for disease modelling and drug discovery. Nat Rev Drug Discov. 2011;10:915–29.

    CAS  PubMed  Google Scholar 

  33. Diecke S, Diecke S, Diecke S, Jung SM, Lee J, Lee J, et al. Recent technological updates and clinical applications of induced pluripotent stem cells. Korean J Intern Med. 2014;29:547–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Chou BK, Mali P, Huang X, Ye Z, Dowey SN, Resar LMS, et al. Efficient human iPS cell derivation by a non-integrating plasmid from blood cells with unique epigenetic and gene expression signatures. Cell Res. 2011;21:518–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;107:861–72.

    Article  Google Scholar 

  36. Pietronave S, Prat M. Advances and applications of induced pluripotent stem cells. Can J Physiol Pharmacol. 2012;90:317–25.

    Article  CAS  PubMed  Google Scholar 

  37. Schlaeger T. Nonintegrating human somatic cell reprogramming methods. Adv Biochem Eng Biotechnol. 2018;163:1–21.

    Google Scholar 

  38. Parameswaran S, Balasubramanian S, Rao MS, Ahmad I. Concise review: non-cell autonomous reprogramming: a nucleic acid-free approach to induction of pluripotency. Stem Cells. 2011;29:1013–20.

    Article  CAS  PubMed  Google Scholar 

  39. Kelaini S, Cochrane A, Margariti A. Direct reprogramming of adult cells: avoiding the pluripotent state. Stem Cells Cloning. 2014;7:19–29.

    PubMed  PubMed Central  Google Scholar 

  40. Blazejewska EA, Schlötzer-Schrehardt U, Zenkel M, Bachmann B, Chankiewitz E, Jacobi C, et al. Corneal limbal microenvironment can induce transdifferentiation of hair follicle stem cells into corneal epithelial-like cells. Stem Cells. 2009;27:642–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Meyer-Blazejewska EA, Call MK, Yamanaka O, Liu H, Schlötzer-Schrehardt U, Kruse FE, et al. From hair to cornea: toward the therapeutic use of hair follicle-derived stem cells in the treatment of limbal stem cell deficiency. Stem Cells. 2011;29:57–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Yang K, Jiang Z, Wang D, Lian X, Yang T. Corneal epithelial-like transdifferentiation of hair follicle stem cells is mediated by pax6 and β-catenin/Lef-1. Cell Biol Int. 2009;33:861–6.

    Article  CAS  PubMed  Google Scholar 

  43. Saichanma S, Bunyaratvej A, Sila-Asna M. In vitro transdifferentiation of corneal epithelial-like cells from human skin-derived precursor cells. Int J Ophthalmol. 2012;5:158–63.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Martínez-Conesa EM, Espel E, Reina M, Casaroli-Marano RP. Characterization of ocular surface epithelial and progenitor cell markers in human adipose stromal cells derived from lipoaspirates. Invest Ophthalmol Vis Sci. 2012;53:513–20.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Cieślar-Pobuda A, Rafat M, Knoflach V, Skonieczna M, Hudecki A, Małecki A, et al. Human induced pluripotent stem cell differentiation and direct transdifferentiation into corneal epithelial-like cells. Oncotarget. 2016;7:42314–29.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Mandai M, Watanabe A, Kurimoto Y, Hirami Y, Morinaga C, Daimon T, et al. Autologous induced stem-cell–derived retinal cells for macular degeneration. N Engl J Med. 2017;376:1038–46.

    Article  CAS  PubMed  Google Scholar 

  47. Takashima K, Inoue Y, Tashiro S, Muto K. Lessons for reviewing clinical trials using induced pluripotent stem cells: examining the case of a first-in-human trial for age-related macular degeneration. Regen Med. 2018;13:123–8.

    Article  CAS  PubMed  Google Scholar 

  48. Sugita S, Iwasaki Y, Makabe K, Kimura T, Futagami T, Suegami S, et al. Lack of T cell response to iPSC-derived retinal pigment epithelial cells from HLA homozygous donors. Stem Cell Rep. 2016;7:619–34.

    Article  CAS  Google Scholar 

  49. Sugita S, Iwasaki Y, Makabe K, Kamao H, Mandai M, Shiina T, et al. Successful transplantation of retinal pigment epithelial cells from MHC homozygote iPSCs in MHC-matched models. Stem Cell Rep. 2016;7:635–48.

    Article  CAS  Google Scholar 

  50. Morikawa S, Mabuchi Y, Niibe K, Suzuki S, Nagoshi N, Sunabori T, et al. Development of mesenchymal stem cells partially originate from the neural crest. Biochem Biophys Res Commun. 2009;379:1114–9.

    Article  CAS  PubMed  Google Scholar 

  51. Fuhrmann S. Wnt signaling in eye organogenesis. Organogenesis. 2008;4:60–7.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Mikhailova A, Ilmarinen T, Uusitalo H, Skottman H. Small-molecule induction promotes corneal epithelial cell differentiation from human induced pluripotent stem cells. Stem Cell Rep. 2014;2:219–31.

    Article  CAS  Google Scholar 

  53. Shalom-Feuerstein R, Serror L, De La Forest Divonne S, Petit I, Aberdam E, Camargo L, et al. Pluripotent stem cell model reveals essential roles for miR-450b-5p and miR-184 in embryonic corneal lineage specification. Stem Cells. 2012;30:898–909.

    Article  CAS  PubMed  Google Scholar 

  54. Xu S. microRNA expression in the eyes and their significance in relation to functions. Prog Retin Eye Res. 2009;28:87–116.

    Article  PubMed  Google Scholar 

  55. Rassi D, De Paiva C, Dias L, Modulo C, Adriano L, Fantucci M, et al. Review: microRNAs in ocular surface and dry eye diseases. Ocul Surf. 2017;14:660–9.

    Article  Google Scholar 

  56. Aberdam E, Petit I, Sangari L, Aberdam D. Induced pluripotent stem cell-derived limbal epithelial cells (LiPSC) as a cellular alternative for in vitro ocular toxicity testing. PLoS One. 2017;12:e0179913.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Gonzalez S, Chen L, Deng S. Comparative study of xenobiotic-free media for the cultivation of human limbal epithelial stem/progenitor cells. Tissue Eng Part C Methods. 2017;23:219–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Lancaster MA, Knoblich JA. Organogenesis in a dish: modeling development and disease using organoid technologies. Science. 2014;345:1247125.

    Article  PubMed  Google Scholar 

  59. Kuwahara A, Ozone C, Nakano T, Saito K, Eiraku M, Sasai Y. Generation of a ciliary margin-like stem cell niche from self-organizing human retinal tissue. Nat Commun. 2015;6:6286.

    Article  CAS  PubMed  Google Scholar 

  60. Völkner M, Zschätzsch M, Rostovskaya M, Overall RW, Busskamp V, Anastassiadis K, et al. Retinal organoids from pluripotent stem cells efficiently recapitulate retinogenesis. Stem Cell Rep. 2016;6:525–38.

    Article  Google Scholar 

  61. Foster JW, Wahlin K, Adams SM, Birk DE, Zack DJ, Chakravarti S. Cornea organoids from human induced pluripotent stem cells. Sci Rep. 2017;7:41286.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Hayashi R, Ishikawa Y, Sasamoto Y, Katori R, Nomura N, Ichikawa T, et al. Co-ordinated ocular development from human iPS cells and recovery of corneal function. Nature. 2016;531:376–80.

    Article  CAS  PubMed  Google Scholar 

  63. Hayashi R, Ishikawa Y, Katori R, Sasamoto Y, Taniwaki Y, Takayanagi H, et al. Coordinated generation of multiple ocular-like cell lineages and fabrication of functional corneal epithelial cell sheets from human iPS cells. Nat Protoc. 2017;12:683–96.

    Article  CAS  PubMed  Google Scholar 

  64. Susaimanickam PJ, Maddileti S, Pulimamidi VK, Boyinpally SR, Naik RR, Naik MN, et al. Generating minicorneal organoids from human induced pluripotent stem cells. Development. 2017;144:2338–51.

    Article  CAS  PubMed  Google Scholar 

  65. Zhu Q, Lu Q, Gao R, Cao T. Prospect of human pluripotent stem cell-derived neural crest stem cells in clinical application. Stem Cells Int. 2016;2016:7695836.

    PubMed  PubMed Central  Google Scholar 

  66. Naylor RW, McGhee CNJ, Cowan CA, Davidson AJ, Holm TM, Sherwin T. Derivation of corneal keratocyte-like cells from human induced pluripotent stem cells. PLoS One. 2016;11:e0165464.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Fukuta M, Nakai Y, Kirino K, Nakagawa M, Sekiguchi K, Nagata S, et al. Derivation of mesenchymal stromal cells from pluripotent stem cells through a neural crest lineage using small molecule compounds with defined media. PLoS One. 2014;9:e112291.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Aharony I, Michowiz S, Goldenberg-Cohen N. The promise of stem cell-based therapeutics in ophthalmology. Neural Regen Res. 2017;12:173–80.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Zarbin M. Cell-based therapy for degenerative retinal disease. Trends Mol Med. 2016;22:115–34.

    Article  PubMed  Google Scholar 

  70. Palomo ABA, Lucas M, Dilley RJ, McLenachan S, Chen FK, Requena J, et al. The power and the promise of cell reprogramming: personalized autologous body organ and cell transplantation. J Clin Med. 2014;3:373–87.

    Article  CAS  PubMed  Google Scholar 

  71. Kao WWY, Coulson-Thomas VJ. Cell therapy of corneal diseases. Cornea. 2016;35:S9–19.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Erbani J, Aberdam D, Larghero J, Vanneaux V. Pluripotent stem cells and other innovative strategies for the treatment of ocular surface diseases. Stem Cell Rev. 2016;12:171–8.

    Article  CAS  Google Scholar 

  73. Angunawela RI, Mehta JS, Daniels JT. Ex-vivo ocular surface stem cell therapies: current techniques, applications, hurdles and future directions. Expert Rev Mol Med. 2013;15:e4.

    Article  PubMed  Google Scholar 

  74. Menzel-Severing J, Kruse FE, Schlötzer-Schrehardt U. Stem cell–based therapy for corneal epithelial reconstruction: present and future. Can J Ophthalmol. 2013;48:13–21.

    Article  PubMed  Google Scholar 

  75. Di Iorio E, Ferrari S, Fasolo A, Böhm E, Ponzin D, Barbaro V. Techniques for culture and assessment of limbal stem cell grafts. Ocul Surf. 2010;8:146–53.

    Article  PubMed  Google Scholar 

  76. Morrison M, Bell J, George C, Harmon S, Munsie M, Kaye J. The European General Data Protection Regulation: challenges and considerations for iPSC researchers and biobanks. Regen Med. 2017;12:693–703.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Colombo M, Raposo G, Théry C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol. 2014;30:255–89.

    Article  CAS  PubMed  Google Scholar 

  78. Zhang J, Li S, Li L, Li M, Guo C, Yao J, et al. Exosome and exosomal microRNA: trafficking, sorting, and function. Genomics Proteomics Bioinformatics. 2015;13:17–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Klingeborn M, Dismuke WM, Bowes Rickman C, Stamer WD. Roles of exosomes in the normal and diseased eye. Prog Retin Eye Res. 2017;59:158–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Yu B, Zhang X, Li X. Exosomes derived from mesenchymal stem cells. Int J Mol Sci. 2014;15:4142–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The author acknowledges support from Fundació Marató TV3 (120630-31) and Fondo de Investigaciones Sanitarias del Instituto de Salud Carlos III (FIS14-PI00196 and FIS18-PI00355), from the European Regional Development Fund (FEDER) of European Union.

Compliance with ethical requirements: Ricardo Pedro Casaroli-Marano declares that he has no conflict of interest. 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. No animal studies were carried out by the authors for this article.

Author information

Authors and Affiliations

  1. Department of Surgery, School of Medicine and Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain

    Ricardo Pedro Casaroli-Marano

  2. Institute of Biomedical Research (IIB-Sant Pau) and Barcelona Tissue Bank, Banc de Sang i Teixits, Barcelona, Spain

    Ricardo Pedro Casaroli-Marano

Authors
  1. Ricardo Pedro Casaroli-Marano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ricardo Pedro Casaroli-Marano .

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

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Casaroli-Marano, R.P. (2019). Cell-based Therapy Using Induced Plutipotent Stem Cell. 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_18

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-01304-2_18

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-01303-5

  • Online ISBN: 978-3-030-01304-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation