Skip to main content
SpringerLink
Log in

Controversies in Corneal Epithelial Stem Cell Biology

  • Chapter
  • First Online:
Adult and Embryonic Stem Cells

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

  • 1352 Accesses

Abstract

The loss or dysfunction of corneal epithelial stem cells, or limbal stem cells as they are more commonly known, results in the painful and blinding disease of limbal stem cell deficiency. In 1997, it was proposed that limbal stem cell deficiency could be treated by transplanting cultured limbal stem cells containing human limbal epithelium. The area of limbal stem cell biology therefore now encompasses not only the basic science of stem cell biology but also the area of translational research and cell therapeutics. Ranging from the laboratory to the clinic, there are still many controversies in limbal stem cell biology. In this chapter we describe and outline some of the questions that remain to be answered.

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 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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

  • Ahmad S, Figueiredo F, Lako M (2006) Corneal epithelial stem cells: characterization, culture and transplantation. Regen Med 1(1):29–44

    Article  PubMed  CAS  Google Scholar 

  • Ahmad S et al (2010a) Stem cell therapies for ocular surface disease. Drug Discov Today 15(7–8):306–313

    Article  PubMed  CAS  Google Scholar 

  • Ahmad S et al (2010b) The culture and transplantation of human limbal stem cells. J Cell Physiol 225(1):15–19

    Article  PubMed  CAS  Google Scholar 

  • Armstrong L et al (2004) Phenotypic characterization of murine primitive hematopoietic progenitor cells isolated on basis of aldehyde dehydrogenase activity. Stem Cells 22:1142–1151

    Article  PubMed  Google Scholar 

  • Barbaro V et al (2007) C/EBPdelta regulates cell cycle and self-renewal of human limbal stem cells. J Cell Biol 177(6):1037–1049

    Article  PubMed  CAS  Google Scholar 

  • Bian F et al (2010) Molecular signatures and biological pathway profiles of human corneal epithelial progenitor cells. Int J Biochem Cell Biol 42(7):1142–1153

    Article  PubMed  CAS  Google Scholar 

  • Blazejewska EA et al (2009) Corneal limbal microenvironment can induce transdifferentiation of hair follicle stem cells into corneal epithelial-like cells. Stem Cells 27(3):642–652

    Article  PubMed  CAS  Google Scholar 

  • Budak MT et al (2005) Ocular surface epithelia contain ABCG2-dependent side population cells exhibiting features associated with stem cells. J Cell Sci 118(Pt 8):1715–1724

    Article  PubMed  CAS  Google Scholar 

  • Chacko DM et al (2003) Transplantation of ocular stem cells: the role of injury in incorporation and differentiation of grafted cells in the retina. Vision Res 43(8):937–946

    Article  PubMed  Google Scholar 

  • Cotsarelis G et al (1989) Existence of slow-cycling limbal epithelial basal cells that can be preferentially stimulated to proliferate: implications on epithelial stem cells. Cell 57(2):201–209

    Article  PubMed  CAS  Google Scholar 

  • Daniels JT et al (2006) Stem cell therapy delivery: treading the regulatory tightrope. Regen Med 1(5):715–719

    Article  PubMed  Google Scholar 

  • Davanger M, Evensen A (1971) Role of the pericorneal papillary structure in renewal of corneal epithelium. Nature 229(5286):560–561

    Article  PubMed  CAS  Google Scholar 

  • Daya SM et al (2005) Outcomes and DNA analysis of ex vivo expanded stem cell allograft for ocular surface reconstruction. Ophthalmology 112(3):470–477

    Article  PubMed  Google Scholar 

  • de Paiva CS et al (2005) ABCG2 transporter identifies a population of clonogenic human limbal epithelial cells. Stem Cells 23(1):63–73

    Article  PubMed  Google Scholar 

  • DeSousa JL, Daya S, Malhotra R (2009) Adnexal surgery in patients undergoing ocular surface stem cell transplantation. Ophthalmology 116(2):235–242

    Article  PubMed  Google Scholar 

  • Di Iorio E et al (2005) Isoforms of deltaNp63 and the migration of ocular limbal cells in human corneal regeneration. Proc Natl Acad Sci USA 102(27):9523–9528

    Article  PubMed  Google Scholar 

  • Di Iorio E et al (2006) Q-FIHC: quantification of fluorescence immunohistochemistry to analyse p63 isoforms and cell cycle phases in human limbal stem cells. Microsc Res Tech 69:983–991

    Article  PubMed  Google Scholar 

  • Dua HS et al (2005) Limbal epithelial crypts: a novel anatomical structure and a putative limbal stem cell niche. Br J Ophthalmol 89(5):529–532

    Article  PubMed  CAS  Google Scholar 

  • Espana EM et al (2002) Idiopathic limbal stem cell deficiency. Ophthalmology 109(11): 2004–2010

    Article  PubMed  Google Scholar 

  • Geerling G, Maclennan S, Hartwig D (2004) Autologous serum eye drops for ocular surface disorders. Br J Ophthalmol 88(11):1467–1474

    Article  PubMed  CAS  Google Scholar 

  • Gomes JA et al (2010) Corneal reconstruction with tissue-engineered cell sheets composed of human immature dental pulp stem cells. Invest Ophthalmol Vis Sci 51(3):1408–1414

    Article  PubMed  Google Scholar 

  • Grueterich M, Espana E, Tseng SC (2002) Connexin 43 expression and proliferation of human limbal epithelium on intact and denuded amniotic membrane. Invest Ophthalmol Vis Sci 43(1):63–71

    PubMed  Google Scholar 

  • Grueterich M, Espana EM, Tseng SC (2003a) Ex vivo expansion of limbal epithelial stem cells: amniotic membrane serving as a stem cell niche. Surv Ophthalmol 48(6):631–646

    Article  PubMed  Google Scholar 

  • Grueterich M, Espana EM, Tseng SC (2003b) Modulation of keratin and connexin expression in limbal epithelium expanded on denuded amniotic membrane with and without a 3T3 fibroblast feeder layer. Invest Ophthalmol Vis Sci 44(10):4230–4236

    Article  PubMed  Google Scholar 

  • Henderson TR et al (1997) Do transplanted corneal limbal stem cells survive in vivo long-term? Possible techniques to detect donor cell survival by polymerase chain reaction with the amelogenin gene and Y-specific probes. Eye (Lond) 11(Pt 6):779–785

    Article  Google Scholar 

  • Henderson TR et al (2001a) Identifying the origin of single corneal cells by DNA fingerprinting. Part I. Implications for corneal limbal allografting. Cornea 20(4):400–403

    Article  PubMed  CAS  Google Scholar 

  • Henderson TR et al (2001b) Identifying the origin of single corneal cells by DNA fingerprinting. Part II. Application to limbal allografting. Cornea 20(4):404–407

    Article  PubMed  CAS  Google Scholar 

  • Inatomi T et al (2006) Midterm results on ocular surface reconstruction using cultivated autologous oral mucosal epithelial transplantation. Am J Ophthalmol 141(2):267–275

    Article  PubMed  Google Scholar 

  • Kenyon KR, Rapoza PA (1995) Limbal allograft transplantation for ocular surface disorders. Ophthalmology 102(Suppl):101–102

    Google Scholar 

  • Kenyon KR, Tseng SC (1989) Limbal autograft transplantation for ocular surface disorders. Ophthalmology 96(5):709–722, discussion 722–3

    PubMed  CAS  Google Scholar 

  • Koizumi N et al (2000) Cultivation of corneal epithelial cells on intact and denuded human amniotic membrane. Invest Ophthalmol Vis Sci 41(9):2506–2513

    PubMed  CAS  Google Scholar 

  • Koizumi N et al (2002) An evaluation of cultivated corneal limbal epithelial cells, using cell-­suspension culture. Invest Ophthalmol Vis Sci 43(7):2114–2121

    PubMed  Google Scholar 

  • Kolli S et al (2010) Successful clinical implementation of corneal epithelial stem cell therapy for treatment of unilateral limbal stem cell deficiency. Stem Cells 28(3):597–610

    PubMed  CAS  Google Scholar 

  • Kruse FE, Tseng SC (1991) A serum-free clonal growth assay for limbal, peripheral, and central corneal epithelium. Invest Ophthalmol Vis Sci 32(7):2086–2095

    PubMed  CAS  Google Scholar 

  • Kruse FE, Tseng SC (1992) Proliferative and differentiative response of corneal and limbal epithelium to extracellular calcium in serum-free clonal cultures. J Cell Physiol 151(2):347–360

    Article  PubMed  CAS  Google Scholar 

  • Kurpakus MA, Stock EL, Jones JC (1990) Expression of the 55-kD/64-kD corneal keratins in ocular surface epithelium. Invest Ophthalmol Vis Sci 31(3):448–456

    PubMed  CAS  Google Scholar 

  • Ma Y et al (2006) Reconstruction of chemically burned rat corneal surface by bone marrow-derived human mesenchymal stem cells. Stem Cells 24(2):315–321

    Article  PubMed  Google Scholar 

  • Majo F et al (2008) Oligopotent stem cells are distributed throughout the mammalian ocular ­surface. Nature 456(7219):250–254

    Article  PubMed  CAS  Google Scholar 

  • Osei-Bempong C, Henein C, Ahmad S (2009) Culture conditions for primary human limbal ­epithelial cells. Regen Med 4(3):461–470

    Article  PubMed  CAS  Google Scholar 

  • Pellegrini G et al (1997) Long-term restoration of damaged corneal surfaces with autologous ­cultivated corneal epithelium. Lancet 349(9057):990–993

    Article  PubMed  CAS  Google Scholar 

  • Pellegrini G et al (2001) p63 identifies keratinocyte stem cells. Proc Natl Acad Sci USA 98(6): 3156–3161

    Article  PubMed  CAS  Google Scholar 

  • Puangsricharern V, Tseng SC (1995) Cytologic evidence of corneal diseases with limbal stem cell deficiency. Ophthalmology 102(10):1476–1485

    PubMed  CAS  Google Scholar 

  • Qi H et al (2007) Patterned expression of neurotrophic factors and receptors in human limbal and corneal regions. Mol Vis 13:1934–1941

    PubMed  CAS  Google Scholar 

  • Qi H et al (2008) Nerve growth factor and its receptor TrkA serve as potential markers for human corneal epithelial progenitor cells. Exp Eye Res 86(1):34–40

    Article  PubMed  CAS  Google Scholar 

  • Rama P et al (2010) Limbal stem-cell therapy and long-term corneal regeneration. N Engl J Med 363(2):147–155

    Article  PubMed  CAS  Google Scholar 

  • Ramaesh T et al (2003) Corneal abnormalities in Pax6+/− small eye mice mimic human aniridia-related keratopathy. Invest Ophthalmol Vis Sci 44(5):1871–1878

    Article  PubMed  Google Scholar 

  • Ramaesh K et al (2005) Evolving concepts on the pathogenic mechanisms of aniridia related keratopathy. Int J Biochem Cell Biol 37(3):547–557

    Article  PubMed  CAS  Google Scholar 

  • Shortt AJ et al (2007a) Transplantation of ex vivo cultured limbal epithelial stem cells: a review of techniques and clinical results. Surv Ophthalmol 52(5):483–502

    Article  PubMed  Google Scholar 

  • Shortt AJ et al (2007b) Characterization of the limbal epithelial stem cell niche: novel imaging techniques permit in vivo observation and targeted biopsy of limbal epithelial stem cells. Stem Cells 25(6):1402–1409

    Article  PubMed  Google Scholar 

  • Stojkovic M et al (2004) Derivation of human embryonic stem cells from day-8 blastocysts ­recovered after three-step in vitro culture. Stem Cells 22(5):790–797

    Article  PubMed  Google Scholar 

  • Tsai RJ, Li LM, Chen JK (2000) Reconstruction of damaged corneas by transplantation of ­autologous limbal epithelial cells. N Engl J Med 343(2):86–93

    Article  PubMed  CAS  Google Scholar 

  • Wolosin JM et al (2002) Changes in connexin43 in early ocular surface development. Curr Eye Res 24(6):430–438

    Article  PubMed  Google Scholar 

  • Zhang X et al (2005) Comparison of cell-suspension and explant culture of rabbit limbal epithelial cells. Exp Eye Res 80(2):227–233

    Article  PubMed  CAS  Google Scholar 

  • Zhao X et al (2002) Adult corneal limbal epithelium: a model for studying neural potential of non-neural stem cells/progenitors. Dev Biol 250(2):317–331

    Article  PubMed  CAS  Google Scholar 

  • Zhao X et al (2008) Derivation of neurons with functional properties from adult limbal epithelium: implications in autologous cell therapy for photoreceptor degeneration. Stem Cells 26(4): 939–949

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Human Genetics, Newcastle University, Newcastle upon Tyne, UK

    Haifa Ali, Charles Osei-Bempong, Ani Ray-Chaudhuri, Arianna Bianchi, Mohit Parekh & Sajjad Ahmad

  2. North East England Stem Cell Institute, Newcastle University, Newcastle upon Tyne, UK

    Haifa Ali, Charles Osei-Bempong, Ani Ray-Chaudhuri, Arianna Bianchi, Mohit Parekh & Sajjad Ahmad

  3. Advanced Medical and Dental Institute, Universiti Sains Malaysia, Penang, Malaysia

    Bakiah Shaharuddin

  4. Royal Victoria Infirmary, Newcastle upon Tyne, UK

    Sajjad Ahmad

  5. Department of Ophthalmology, Newcastle University, Newcastle upon Tyne, UK

    Sajjad Ahmad

  6. Institute of Human Genetics, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK

    Sajjad Ahmad

Authors
  1. Haifa Ali
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Charles Osei-Bempong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ani Ray-Chaudhuri
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bakiah Shaharuddin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Arianna Bianchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mohit Parekh
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sajjad Ahmad
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sajjad Ahmad .

Editor information

Editors and Affiliations

  1. Smyth Rd 501, Ottawa, K1H 8L6, Canada

    Kursad Turksen

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Ali, H. et al. (2012). Controversies in Corneal Epithelial Stem Cell Biology. In: Turksen, K. (eds) Adult and Embryonic Stem Cells. Stem Cell Biology and Regenerative Medicine. Humana Press. https://doi.org/10.1007/978-1-61779-630-2_9

Download citation

Publish with us

Policies and ethics

Search

Navigation