Skip to main content

Cellular Therapy for Ocular Diseases

  • Chapter
  • First Online:
Pharmacology of Ocular Therapeutics
  • 1585 Accesses

Abstract

Over the past decade several investigations have been performed to study the regenerative capacity of different type of stem cells such as adult and embryonic stem cells for their application in Opthalmology. In particular, limbal epithelial stem cells have shown most promising results for ocular surface reconstruction. This book chapter discusses current approaches used in stem cell therapy and the challenges faced along with the future scope of advancements to use stem cell in other ocular degenerative conditions.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 54.99
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

  • Arpitha P, Prajna NV, Srinivasan M, Muthukkaruppan V. High expression of p63 combined with a large N/C ratio defines a subset of human limbal epithelial cells: implications on epithelial stem cells. Invest Ophthalmol Vis Sci. 2005;46:3631–6.

    Article  PubMed  Google Scholar 

  • Banin E, Obolensky A, Idelson M, Hemo I, Reinhardtz E, Pikarsky E. Retinal incorporation and differentiation of neural precursors derived from human embryonic stem cells. Stem Cells. 2006;24(2):246–57.

    Article  PubMed  Google Scholar 

  • Blazejewska EA, Schlotzer-Schrehardt U, Zenkel M, Bachmann B, Chankiewitz E, Jacobi C. Corneal limbal microenvironment can induce transdifferentiation of hair follicle stem cells into corneal epithelial-like cells. Stem Cells. 2009;27(3):642–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Borrelli M, Reichl S, Feng Y, Schargus M, Schrader S, Geerling G. In vitro characterization and ex vivo surgical evaluation of human hair keratin films in ocular surface reconstruction after sterilization processing. J Mater Sci Mater Med. 2013;24(1):221–30.

    Article  CAS  PubMed  Google Scholar 

  • Bray LJ, George KA, Ainscough SL, Hutmacher DW, Chirila TV, Harkin DG. Human corneal epithelial equivalents constructed on Bombyx mori silk fibroin membranes. Biomaterials. 2011;32(22):5086–91.

    Article  CAS  PubMed  Google Scholar 

  • Budak MT, Alpdogan OS, Zhou M, Lavker RM, Akinci MA, Wolosin JM. Ocular surface epithelia contain ABCG2-dependent side population cells exhibiting features associated with stem cells. J Cell Sci. 2005;118:1715–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carr AJ, Vugler AA, Hikita ST, Lawrence JM, Gias C, Chen LL. Protective effects of human iPS-derived retinal pigment epithelium cell transplantation in the retinal dystrophic rat. PLoS One. 2009;4:e8152.

    Article  PubMed  PubMed Central  Google Scholar 

  • Cotsarelis G, Cheng SZ, Dong G, Sun TT, Lavker RM. Existence of slow-cycling limbal epithelial basal cells that can be preferentially stimulated to proliferate: implications on epithelial stem cells. Cell. 1989;57(2):201–9.

    Article  CAS  PubMed  Google Scholar 

  • De Paiva CS, Chen Z, Corrales RM, Pflugfelder SC, Li DQ. ABCG2 transporter identifies a population of clonogenic human limbal epithelial cells. Stem Cells. 2005;23(1):63–73.

    Article  PubMed  PubMed Central  Google Scholar 

  • Di Girolamo N, Chui J, Wakefield D, Coroneo MT. Cultured human ocular surface epithelium on therapeutic contact lenses. Br J Ophthalmol. 2007;91:459–64.

    Article  PubMed  PubMed Central  Google Scholar 

  • Di Iorio E, Barbaro V, Ruzza A, Ponzin D, Pellegrini G, De Luca M. Isoforms of DeltaNp63 and the migration of ocular limbal cells in human corneal regeneration. Proc Natl Acad Sci U S A. 2005;102(27):9523–8.

    Article  PubMed  PubMed Central  Google Scholar 

  • Dravida S, Gaddipati S, Griffith M, Merrett K, Lakshmi Madhira S, Sangwan VS. A biomimetic scaffold for culturing limbal stem cells: a promising alternative for clinical transplantation. J Tissue Eng Regen Med. 2008;2(5):263–71.

    Article  CAS  PubMed  Google Scholar 

  • Feng Y, Borrelli M, Meyer-Ter-Vehn T, Reichl S, Schrader S, Geerling G. Epithelial wound healing on keratin film, amniotic membrane and polystyrene in vitro. Curr Eye Res. 2014;39(6):561–70.

    Article  CAS  PubMed  Google Scholar 

  • Goldberg MF, Bron AJ. Limbal palisades of Vogt. Trans Am Ophthalmol Soc. 1982;80:155–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Grolik M, Szczubialka K, Wowra B, Dobrowolski D, Orzechowska-WylÄ™gaÅ‚a B, WylÄ™gaÅ‚a E. Hydrogel membranes based on genipin-cross-linked chitosan blends for corneal epithelium tissue engineering. J Mater Sci Mater Med. 2012;23(8):1991–2000.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Han B, Schwab IR, Madsen TK, Isseroff RR. A fibrin-based bioengineered ocular surface with human corneal epithelial stem cells. Cornea. 2002;21(5):505–10.

    Article  PubMed  Google Scholar 

  • Hirano M, Yamamoto A, Yoshimura N, Tokunaga T, Motohashi T, Ishizaki K. Generation of structures formed by lens and retinal cells differentiating from embryonic stem cells. Dev Dyn. 2003;228(4):664–71.

    Article  PubMed  Google Scholar 

  • Huang T, Wang Y, Zhang H, Gao H, Hu A. Limbal allografting from living related donors to treat partial limbal deficiency secondary to ocular chemical burns. Arch Ophthalmol. 2011;129(10):1267–73.

    Article  PubMed  Google Scholar 

  • Jin M, Li S, Moghrabi WN, Sun H, Travis GH. Rpe65 is the retinoid isomerase in bovine retinal pigment epithelium. Cell. 2005;122(3):449–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kenyon KR, Tseng SC. Limbal autograft transplantation for ocular surface disorders. Ophthalmology. 1989;96(5):709–22.

    Article  CAS  PubMed  Google Scholar 

  • Kumar A, Mohnaraj SN, Mochi TB, Mohanty S, Seth T, Azad R. Assessment of central retinal function after autologous bone marrow derived intravitreal stem cell injection in patients with retinitis pigmentosa using multifocal ERG: a pilot study. World J Retina Vitreous. 2012;2(1):5–13.

    Article  Google Scholar 

  • Kuno N, Fujii S. Ocular drug delivery systems for the posterior segment: A review. Retina Today (May/June) 2012;54–9.

    Google Scholar 

  • Lagali N, Eden U, Utheim TP, Chen X, Riise R, Dellby A, Fagerholm P. In vivo morphology of the limbal palisades of Vogt correlates with progressive stem cell deficiency in aniridia-related keratopathy. Invest Ophthalmol Vis Sci. 2013;54:5333–42.

    Article  PubMed  Google Scholar 

  • Lam DS, Young AL, Leung AT, Fan DS, Wong AK. Limbal stem cell allografting from related live donors for corneal surface reconstruction. Ophthalmology. 2000;107(7):411–2.

    Article  CAS  PubMed  Google Scholar 

  • Ma Y, Xu Y, Xiao Z, Yang W, Zhang C, Song E. Reconstruction of chemically burned rat corneal surface by bone marrow-derived human mesenchymal stem cells. Stem Cells. 2006;24:315–21.

    Article  PubMed  Google Scholar 

  • McIntosh Ambrose W, Salahuddin A, So S, Ng S, Ponce Márquez S, Takezawa T. Collagen Vitrigel membranes for the in vitro reconstruction of separate corneal epithelial, stromal, and endothelial cell layers. J Biomed Mater Res B Appl Biomater. 2009;90(2):818–31.

    Article  PubMed  Google Scholar 

  • Meallet MA, Espana EM, Grueterich M, Ti SE, Goto E, Tseng SC. Amniotic membrane transplantation with conjunctival limbal autograft for total limbal stem cell deficiency. Ophthalmology. 2003;110(8):1585–92.

    Article  PubMed  Google Scholar 

  • Mittal V, Sangwan VS, Fernandes M, Thomas R. Survival analysis of conjunctival limbal grafts and amniotic membrane transplantation in eyes with total limbal stem cell deficiency. Am J Ophthalmol. 2006;141:599–600.

    Article  PubMed  Google Scholar 

  • Nakamura T, Takeda K, Inatomi T. Long-term results of autologous cultivated oral mucosal epithelial transplantation in the scar phase of severe ocular surface disorders. Br J Ophthalmol. 2011;95:942–6.

    Article  PubMed  Google Scholar 

  • Ohyama M. Hair follicle bulge: a fascinating reservoir of epithelial stem cells. J Dermatol Sci. 2007;46:81–9.

    Article  CAS  PubMed  Google Scholar 

  • Ohyama M, Terunuma A, Tock CL, Radonovich MF, Pise-Masison CA, Hopping SB. Characterization and isolation of stem cell-enriched human hair follicle bulge cells. J Clin Invest. 2006;116(1):249–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Otani A, Dorrell MI, Kinder K, Moreno SK, Nusinowitz S, Banin E, Heckenlively J. Rescue of retinal degeneration by intravitreally injected adult bone marrow-derived lineage-negative hematopoietic stem cells. J Clin Invest. 2004;114(6):765–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pellegrini G, Golisano O, Paterna P, Lambiase A, Bonini S, Rama P. Location and clonal analysis of stem cells and their differentiated progeny in the human ocular surface. J Cell Biol. 1999;145(4):769–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rama P, Bonini S, Lambiase A, Golisano O, Paterna P, De Luca M. Autologous fibrin-cultured limbal stem cells permanently restore the corneal surface of patients with total limbal stem cell deficiency. Transplantation. 2001;72(9):1478–85.

    Article  CAS  PubMed  Google Scholar 

  • Rao SK, Rajagopal R, Sitalakshmi G, Padmanabhan P. Limbal allografting from related live donors for corneal surface reconstruction. Ophthalmology. 1999;106:822–8.

    Article  CAS  PubMed  Google Scholar 

  • Sangwan VS, Basu S, MacNeil S, Balasubramanian D. Simple limbal epithelial transplantation (SLET): a novel surgical technique for the treatment of unilateral limbal stem cell deficiency. Br J Ophthalmol. 2012;96:931–4.

    Article  PubMed  Google Scholar 

  • Schermer A, Galvin S, Sun TT. Differentiation-related expression of a major 64K corneal keratin in vivo and in culture suggests limbal location of corneal epithelial stem cells. J Cell Biol. 1986;103(1):49–62.

    Article  CAS  PubMed  Google Scholar 

  • Schwartz SD, Hubschman JP, Heilwell G, Franco-Cardenas V, Pan CK, Ostrick RM. Embryonic stem cell trials for macular degeneration: a preliminary report. Lancet. 2012;379(25):713–20.

    Article  CAS  PubMed  Google Scholar 

  • Sen S, Sharma S, Gupta A, Gupta N, Singh N, Roychoudhury A. Molecular characterization of explant cultured human oral mucosal epithelial cells. Invest Ophthalmol Vis Sci IOVS. 2011;52(13):9548–54.

    Article  CAS  Google Scholar 

  • Shanmuganathan VA, Foster T, Kulkarni BB, Hopkinson A, Gray T, Powe DG, Lowe J, Dua HS. Morphological characteristics of the limbal epithelial crypt. Br J Ophthalmol. 2007;91(4):514–9.

    Article  PubMed  PubMed Central  Google Scholar 

  • Sharma S, Mohanty S, Gupta D, Jassal M, Agrawal AK, Tandon R. Cellular response of limbal epithelial cells on electrospun poly-ε- caprolactone nanofibrous scaffolds for ocular surface bioengineering: a preliminary in vitro study. Mol Vis. 2011a;17:2898–910.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sharma S, Tandon R, Mohanty S, Sharma N, Vanathi M, Sen S. Culture of corneal limbal epithelial stem cells: experience from benchtop to bedside in a tertiary care hospital in India. Cornea. 2011b;30:1223–32.

    Article  PubMed  Google Scholar 

  • Takezawa T, Ozaki K, Nitani A, Takabayashi C, Shimo-Oka T. Collagen vitrigel: a novel scaffold that can facilitate a three-dimensional culture for reconstructing organoids. Cell Transplant. 2004;13(4):463–73.

    Article  PubMed  Google Scholar 

  • Talbot M, Carrier P, Giasson CJ, Deschambeault A, Guérin SL, Auger FA. Autologous transplantation of rabbit limbal epithelia cultured on fibrin gels for ocular surface reconstruction. Mol Vis. 2006;12:65–75.

    CAS  PubMed  Google Scholar 

  • Tsubota K, Satake Y, Kaido M, Shinozaki N, Shimmura S, Bissen-Miyajima H. Treatment of severe ocular surface disorders with corneal epithelial stem cell transplantation. N Engl J Med. 1999;340:1697–703.

    Article  CAS  PubMed  Google Scholar 

  • Ye J, Lee SK, Kook KH, Yoa K. Bone marrow-derived progenitor cells promote corneal wound healing following alkali injury. Graefes Arch Clin Exp Ophthalmol. 2008;246(2):217–22.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sujata Mohanty PhD .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Mohanty, S. (2016). Cellular Therapy for Ocular Diseases. In: Velpandian, T. (eds) Pharmacology of Ocular Therapeutics. Adis, Cham. https://doi.org/10.1007/978-3-319-25498-2_18

Download citation

Publish with us

Policies and ethics