Stem Cell Reviews and Reports

, Volume 7, Issue 2, pp 256–268

Tissue-Regenerating, Vision-Restoring Corneal Epithelial Stem Cells

Article

Abstract

The cornea, the most anterior segment of the eye, provides us with exquisite vision. Unlike other vital tissues, it is poorly protected from the environment and is thus reliant on a self-renewal program to preserve integrity. This function is reserved for corneal epithelial stem cells located in the basal layer of the limbus, a narrow transition zone that segregates the peripheral cornea from the adjacent conjunctiva. Under physiological conditions, these cells replenish the corneal epithelium when mature or traumatized cells are lost. However, when the limbus is extensively damaged, stem cell activity is compromised, resulting in a condition known as limbal stem cell deficiency (LSCD). This disease is characterized by corneal neovascularization and persistent epithelial defects which impair vision. Over the past 20 years a myriad of treatment options have been developed for LSCD, most of which incorporate stem cell transplantation. Due to the disadvantages associated with the use of allogeneic and xenogeneic material, researchers are currently focusing on refining techniques involving autologous limbal tissue transplantation and are delving into the possibility that stem cells found in other organs can provide an alternative source of corneal epithelium. Determining where donor stem cells reside on the recipient’s ocular surface and how long they remain viable will provide further insights into improving current therapeutic options for patients with LSCD.

Keywords

Ocular surface Stem cells Contact lens Epithelial cells Limbus 

References

  1. 1.
    Smith, T. W. (1977). Corneal topography. Doc Ophthalmol, 43(2), 249–76.PubMedGoogle Scholar
  2. 2.
    Obata, H. M. D. P., & Tsuru, T. M. D. (2007). Corneal wound healing from the perspective of keratoplasty specimens with special reference to the function of the Bowman Layer and Descemet Membrane. Cornea, 26(Supplement 1), S82–S9.PubMedGoogle Scholar
  3. 3.
    Maurice, D. M. (1957). The structure and transparency of the cornea. J Physiol, 136(2), 263–86.PubMedGoogle Scholar
  4. 4.
    Rauz, S., & Saw, V. (2010). Serum eye drops, amniotic membrane and limbal epithelial stem cells—tools in the treatment of ocular surface disease. Cell Tissue Bank, 11(1), 13–27.PubMedGoogle Scholar
  5. 5.
    Ang, L. P., & Tan, D. T. (2005). Stem cells of the eye. In A. Bongso & E. H. Lee (Eds.), Stem cells: from bench to bedside (1st ed., pp. 421–41). Jurong East: World Scientific Publishing Co. Pte. Ltd.Google Scholar
  6. 6.
    Inatomi, T., Spurr-Michaud, S., Tisdale, A. S., Zhan, Q., Feldman, S. T., & Gipson, I. K. (1996). Expression of secretory mucin genes by human conjunctival epithelia. Invest Ophthalmol Vis Sci, 37(8), 1684–92.PubMedGoogle Scholar
  7. 7.
    Cotsarelis, G., Cheng, S. Z., Dong, G., Sun, T. T., & Lavker, R. M. (1989). Existence of slow-cycling limbal epithelial basal cells that can be preferentially stimulated to proliferate: Implications on epithelial stem cells. Cell, 57(2), 201–9.PubMedGoogle Scholar
  8. 8.
    Davanger, M., & Evensen, A. (1971). Role of the pericorneal papillary structure in renewal of corneal epithelium. Nature, 229(5286), 560–1.PubMedGoogle Scholar
  9. 9.
    Pellegrini, G., Golisano, O., Paterna, P., et al. (1999). Location and clonal analysis of stem cells and their differentiated progeny in the human ocular surface. J Cell Biol, 145(4), 769–82.PubMedGoogle Scholar
  10. 10.
    Wei, Z. G., Cotsarelis, G., Sun, T. T., & Lavker, R. M. (1995). Label-retaining cells are preferentially located in fornical epithelium: implications on conjunctival epithelial homeostasis. Invest Ophthalmol Vis Sci, 36(1), 236–46.PubMedGoogle Scholar
  11. 11.
    Majo, F., Rochat, A., Nicolas, M., Jaoude, G. A., & Barrandon, Y. (2008). Oligopotent stem cells are distributed throughout the mammalian ocular surface. Nature, 456(7219), 250–4.PubMedGoogle Scholar
  12. 12.
    Maseruka, H., Ridgway, A., Tullo, A., & Bonshek, R. (2000). Developmental changes in patterns of expression of tenascin-c variants in the human cornea. Invest Ophthalmol Vis Sci, 41(13), 4101–7.PubMedGoogle Scholar
  13. 13.
    Pajoohesh-Ganji, A., Ghosh, S. P., & Stepp, M. A. (2004). Regional distribution of α9β1 integrin within the limbus of the mouse ocular surface. Dev Dyn, 230(3), 518–28.PubMedGoogle Scholar
  14. 14.
    Dua, H. S., Miri, A., Alomar, T., Yeung, A. M., & Said, D. G. (2009). The role of limbal stem cells in corneal epithelial maintenance: testing the dogma. Ophthalmology, 116(5), 856–63.PubMedGoogle Scholar
  15. 15.
    Townsend, W. M. (1991). The limbal palisades of Vogt. Trans Am Ophthalmol Soc, 89, 721–56.PubMedGoogle Scholar
  16. 16.
    Notara, M., Alatza, A., Gilfillan, J., et al. (2010). In sickness and in health: corneal epithelial stem cell biology, pathology and therapy. Exp Eye Res, 90(2), 188–95.PubMedGoogle Scholar
  17. 17.
    Thoft, R. A., & Friend, J. (1983). The X, Y, Z hypothesis of corneal epithelial maintenance. Invest Ophthalmol Vis Sci, 24(10), 1442–3.PubMedGoogle Scholar
  18. 18.
    Dua, H. S., Shanmuganathan, V. A., Powell-Richards, A. O., Tighe, P. J., & Joseph, A. (2005). Limbal epithelial crypts: a novel anatomical structure and a putative limbal stem cell niche. Br J Ophthalmol, 89(5), 529–32.PubMedGoogle Scholar
  19. 19.
    Shortt, A. J., Secker, G. A., Munro, P. M., Khaw, P. T., Tuft, S. J., & Daniels, J. T. (2007). 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), 1402–9.PubMedGoogle Scholar
  20. 20.
    Rheinwald, J. G., & Green, H. (1975). Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells. Cell, 6(3), 331–43.PubMedGoogle Scholar
  21. 21.
    Civin, C. I., Strauss, L. C., Brovall, C., Fackler, M. J., Schwartz, J. F., & Shaper, J. H. (1984). Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells. J Immunol, 133(1), 157–65.PubMedGoogle Scholar
  22. 22.
    Pellegrini, G., Dellambra, E., Golisano, O., et al. (2001). p63 identifies keratinocyte stem cells. Proc Natl Acad Sci U S A, 98(6), 3156–61.PubMedGoogle Scholar
  23. 23.
    Yoshida, S., Shimmura, S., Kawakita, T., et al. (2006). Cytokeratin 15 can be used to identify the limbal phenotype in normal and diseased ocular surfaces. Invest Ophthalmol Vis Sci, 47(11), 4780–6.PubMedGoogle Scholar
  24. 24.
    Lauweryns, B., van den Oord, J., De Vos, R., & Missotten, L. (1993). A new epithelial cell type in the human cornea. Invest Ophthalmol Vis Sci, 34(6), 1983–90.PubMedGoogle Scholar
  25. 25.
    Watanabe, K., Nishida, K., Yamato, M., et al. (2004). Human limbal epithelium contains side population cells expressing the ATP-binding cassette transporter ABCG2. FEBS Lett, 565(1), 6–10.PubMedGoogle Scholar
  26. 26.
    Kurpakus, M. A., Stock, E. L., & Jones, J. C. (1990). Expression of the 55-kD/64-kD corneal keratins in ocular surface epithelium. Invest Ophthalmol Vis Sci, 31(3), 448–56.PubMedGoogle Scholar
  27. 27.
    Schermer, A., Galvin, S., & Sun, T. T. (1986). Differentiation-related expression of a major 64 K corneal keratin in vivo and in culture suggests limbal location of corneal epithelial stem cells. J Cell Biol, 103(1), 49–62.PubMedGoogle Scholar
  28. 28.
    Mills, A. A., Zheng, B., Wang, X.-J., Vogel, H., Roop, D. R., & Bradley, A. (1999). p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature, 398(6729), 708–13.PubMedGoogle Scholar
  29. 29.
    Yang, A., Schweitzer, R., Sun, D., et al. (1999). p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development. Nature, 398(6729), 714–8.PubMedGoogle Scholar
  30. 30.
    Di Iorio, E., Barbaro, V., Ruzza, A., Ponzin, D., Pellegrini, G., & De Luca, M. (2005). Isoforms of DeltaNp63 and the migration of ocular limbal cells in human corneal regeneration. Proc Natl Acad Sci U S A, 102(27), 9523–8.PubMedGoogle Scholar
  31. 31.
    Lyle, S., Christofidou-Solomidou, M., Liu, Y., Elder, D. E., Albelda, S., & Cotsarelis, G. (1998). The C8/144B monoclonal antibody recognizes cytokeratin 15 and defines the location of human hair follicle stem cells. J Cell Sci, 111(21), 3179–88.PubMedGoogle Scholar
  32. 32.
    Schlötzer-Schrehardt, U., & Kruse, F. E. (2005). Identification and characterization of limbal stem cells. Exp Eye Res, 81(3), 247–64.PubMedGoogle Scholar
  33. 33.
    Zhou, S., Schuetz, J. D., Bunting, K. D., et al. (2001). The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med, 7(9), 1028–34.PubMedGoogle Scholar
  34. 34.
    Di Girolamo, N., Sarris, M., Chui, J., Cheema, H., Coroneo, M. T., & Wakefield, D. (2008). Localization of the low-affinity nerve growth factor receptor p75 in human limbal epithelial cells. J Cell Mol Med, 12(6b), 2799–811.PubMedGoogle Scholar
  35. 35.
    Botchkarev, V. A., Botchkareva, N. V., Albers, K. M., Chen, L.-H., Welker, P. I. A., & Paus, R. (2000). A role for p75 neurotrophin receptor in the control of apoptosis-driven hair follicle regression. FASEB J, 14(13), 1931–42.PubMedGoogle Scholar
  36. 36.
    Botchkareva, N. V., Botchkarev, V. A., Chen, L.-H., Lindner, G., & Paus, R. (1999). A role for p75 neurotrophin receptor in the control of hair follicle morphogenesis. Dev Biol, 216(1), 135–53.PubMedGoogle Scholar
  37. 37.
    Grueterich, M., Espana, E. M., & Tseng, S. C. G. (2003). Ex vivo expansion of limbal epithelial stem cells: amniotic membrane serving as a stem cell niche. Surv Ophthalmol, 48(6), 631–46.PubMedGoogle Scholar
  38. 38.
    Lambiase, A., Rama, P., Bonini, S., Caprioglio, G., & Aloe, L. (1998). Topical treatment with nerve growth factor for corneal neurotrophic ulcers. N Engl J Med, 338(17), 1174–80.PubMedGoogle Scholar
  39. 39.
    Chee, K. Y. H., Kicic, A., & Wiffen, S. J. (2006). Limbal stem cells: the search for a marker. Clin Experiment Ophthalmol, 34(1), 64–73.PubMedGoogle Scholar
  40. 40.
    Slack, J. M. (2000). Stem cells in epithelial tissues. Science, 287(5457), 1431–3.PubMedGoogle Scholar
  41. 41.
    Clausen, H., Vedtofte, P., Moe, D., Dabelsteen, E., Sun, T.-T., & Dale, B. (1986). Differentiation-dependent expression of keratins in human oral epithelia. J Investig Dermatol, 86(3), 249–54.PubMedGoogle Scholar
  42. 42.
    Nakamura, T., Endo, K., & Kinoshita, S. (2007). Identification of human oral keratinocyte stem/progenitor cells by neurotrophin receptor p75 and the role of neurotrophin/p75 signaling. Stem Cells, 25(3), 628–38.PubMedGoogle Scholar
  43. 43.
    Madhira, S. L., Vemuganti, G., Bhaduri, A., Gaddipati, S., Sangwan, V. S., & Ghanekar, Y. (2008). Culture and characterization of oral mucosal epithelial cells on human amniotic membrane for ocular surface reconstruction. Mol Vis, 14, 189–96.PubMedGoogle Scholar
  44. 44.
    Tao, Q., Qiao, B., Lv, B., Zheng, C., Chen, Z., & Huang, H. (2009). p63 and its isoforms as markers of rat oral mucosa epidermal stem cells in vitro. Cell Biochem Funct, 27(8), 535–41.PubMedGoogle Scholar
  45. 45.
    Nakamura, T., Inatomi, T., Sotozono, C., Amemiya, T., Kanamura, N., & Kinoshita, S. (2004). Transplantation of cultivated autologous oral mucosal epithelial cells in patients with severe ocular surface disorders. Br J Ophthalmol, 88(10), 1280–4.PubMedGoogle Scholar
  46. 46.
    Nishida, K., Yamato, M., Hayashida, Y., et al. (2004). Corneal reconstruction with tissue-engineered cell sheets composed of autologous oral mucosal epithelium. N Engl J Med, 351(12), 1187–96.PubMedGoogle Scholar
  47. 47.
    Chen, H.-C. J., Chen, H.-L., Lai, J.-Y., et al. (2009). Persistence of transplanted oral mucosal epithelial cells in human cornea. Invest Ophthalmol Vis Sci, 50(10), 4660–8.PubMedGoogle Scholar
  48. 48.
    Cotsarelis, G., Sun, T.-T., & Lavker, R. M. (1990). Label-retaining cells reside in the bulge area of pilosebaceous unit: Implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell, 61(7), 1329–37.PubMedGoogle Scholar
  49. 49.
    Blazejewska, E. A., Schlötzer-Schrehardt, U., Zenkel, M., et al. (2009). Corneal limbal microenvironment can induce transdifferentiation of hair follicle stem cells into corneal epithelial-like cells. Stem Cells, 27(3), 642–52.PubMedGoogle Scholar
  50. 50.
    Pearton, D. J., Yang, Y., & Dhouailly, D. (2005). Transdifferentiation of corneal epithelium into epidermis occurs by means of a multistep process triggered by dermal developmental signals. Proc Natl Acad Sci U S A, 102(10), 3714–9.PubMedGoogle Scholar
  51. 51.
    Yang, X., Moldovan, N., Zhao, Q., et al. (2008). Reconstruction of damaged cornea by autologous transplantation of epidermal adult stem cells. Mol Vis, 14, 1064–70.PubMedGoogle Scholar
  52. 52.
    Evans, M. J., Van Winkle, L. S., Fanucchi, M. V., & Plopper, C. G. (2001). Cellular and molecular characteristics of basal cells in airway epithelium. Exp Lung Res, 27, 401–15.PubMedGoogle Scholar
  53. 53.
    Shimizu, T., Nishihara, M., Kawaguchi, S., & Sakakura, Y. (1994). Expression of phenotypic markers during regeneration of rat tracheal epithelium following mechanical injury. Am J Respir Cell Mol Biol, 11(1), 85–94.PubMedGoogle Scholar
  54. 54.
    Rock, J. R., Onaitis, M. W., Rawlins, E. L., et al. (2009). Basal cells as stem cells of the mouse trachea and human airway epithelium. Proc Natl Acad Sci U S A, 106(31), 12771–5.PubMedGoogle Scholar
  55. 55.
    Daniely, Y., Liao, G., Dixon, D., et al. (2004). Critical role of p63 in the development of a normal esophageal and tracheobronchial epithelium. Am J Physiol Cell Physiol, 287(1), C171–81.PubMedGoogle Scholar
  56. 56.
    Pittenger, M. F., Mackay, A. M., Beck, S. C., et al. (1999). Multilineage potential of adult human mesenchymal stem cells. Science, 284(5411), 143–7.PubMedGoogle Scholar
  57. 57.
    Wang, G., Bunnell, B. A., Painter, R. G., et al. (2005). Adult stem cells from bone marrow stroma differentiate into airway epithelial cells: potential therapy for cystic fibrosis. Proc Natl Acad Sci U S A, 102(1), 186–91.PubMedGoogle Scholar
  58. 58.
    Ye, J., Yao, K., & Kim, J. C. (2005). Mesenchymal stem cell transplantation in a rabbit corneal alkali burn model: engraftment and involvement in wound healing. Eye, 20(4), 482–90.Google Scholar
  59. 59.
    Ma, Y., Xu, Y., Xiao, Z., et al. (2006). Reconstruction of chemically burned rat corneal surface by bone marrow-derived human mesenchymal stem cells. Stem Cells, 24(2), 315–21.PubMedGoogle Scholar
  60. 60.
    Gomes, J. A. P., Geraldes Monteiro, B., Melo, G. B., et al. (2010). Corneal Reconstruction with Tissue-Engineered Cell Sheets Composed of Human Immature Dental Pulp Stem Cells. Invest Ophthalmol Vis Sci, 51(3), 1408–14.PubMedGoogle Scholar
  61. 61.
    Monteiro, B. G., Serafim, R. C., Melo, G. B., et al. (2009). Human immature dental pulp stem cells share key characteristic features with limbal stem cells. Cell Prolif, 42(5), 587–94.PubMedGoogle Scholar
  62. 62.
    Liu, Y., Wang, X., & Jin, Y. (2008). Can bone marrow cells give rise to cornea epithelial cells? Med Hypotheses, 71(3), 411–3.PubMedGoogle Scholar
  63. 63.
    Ye, J., Lee, S. Y., Kook, K. H., & Yao, K. (2008). Bone marrow-derived progenitor cells promote corneal wound healing following alkali injury. Graefes Arch Clin Exp Ophthalmol, 246(2), 217–22.PubMedGoogle Scholar
  64. 64.
    Hon, C., Au, W. Y., & Liang, R. H. S. (2004). Conjunctival carcinoma as a novel post-stem cell transplantation malignancy. Bone Marrow Transplant, 34(2), 181–2.PubMedGoogle Scholar
  65. 65.
    Whitcher, J. P., Srinivasan, M., & Upadhyay, M. P. (2001). Corneal blindness: a global perspective. Bull World Health Organ, 79, 214–21.PubMedGoogle Scholar
  66. 66.
    Hill, R. E., Favor, J., Hogan, B. L. M., et al. (1991). Mouse small eye results from mutations in a paired-like homeobox-containing gene. Nature, 354(6354), 522–5.PubMedGoogle Scholar
  67. 67.
    Li, W., Chen, Y. T., Hayashida, Y., et al. (2008). Down-regulation of Pax6 is associated with abnormal differentiation of corneal epithelial cells in severe ocular surface diseases. J Pathol, 214(1), 114–22.PubMedGoogle Scholar
  68. 68.
    Puangsricharern, V., & Tseng, S. C. (1995). Cytologic evidence of corneal diseases with limbal stem cell deficiency. Ophthalmology, 102(10), 1476–85.PubMedGoogle Scholar
  69. 69.
    Shortt, A. J., Secker, G. A., Notara, M. D., et al. (2007). Transplantation of ex vivo cultured limbal epithelial stem cells: a review of techniques and clinical results. Surv Ophthalmol, 52(5), 483–502.PubMedGoogle Scholar
  70. 70.
    Espana, E. M., Di Pascuale, M., Grueterich, M., Solomon, A., & Tseng, S. C. G. (2004). Keratolimbal allograft in corneal reconstruction. Eye, 18(4), 406–17.PubMedGoogle Scholar
  71. 71.
    Di Girolamo, N., Bosch, M., Zamora, K., Coroneo, M. T., Wakefield, D., & Watson, S. L. (2009). A contact lens-based technique for expansion and transplantation of autologous epithelial progenitors for ocular surface reconstruction. Transplantation, 87(10), 1571–8.PubMedGoogle Scholar
  72. 72.
    Hatch, K. M., & Dana, R. (2009). The structure and function of the limbal stem cell and the disease states associated with limbal stem cell deficiency. Int Ophthalmol Clin, 49(1), 43–52.PubMedGoogle Scholar
  73. 73.
    Ambati, B. K., Nozaki, M., Singh, N., et al. (2006). Corneal avascularity is due to soluble VEGF receptor-1. Nature, 443(7114), 993–7.PubMedGoogle Scholar
  74. 74.
    Koizumi, N., Inatomi, T., Suzuki, T., Sotozono, C., & Kinoshita, S. (2001). Cultivated corneal epithelial stem cell transplantation in ocular surface disorders. Ophthalmology, 108(9), 1569–74.PubMedGoogle Scholar
  75. 75.
    Shimazaki, J., Aiba, M., Goto, E., Kato, N., Shimmura, S., & Tsubota, K. (2002). Transplantation of human limbal epithelium cultivated on amniotic membrane for the treatment of severe ocular surface disorders. Ophthalmology, 109(7), 1285–90.PubMedGoogle Scholar
  76. 76.
    Tsai, R. J., Li, L. M., & Chen, J. K. (2000). Reconstruction of damaged corneas by transplantation of autologous limbal epithelial cells. N Engl J Med, 343(2), 86–93.PubMedGoogle Scholar
  77. 77.
    Rama, P., Bonini, S., Lambiase, A., et al. (2001). Autologous fibrin-cultured limbal stem cells permanently restore the corneal surface of patients with total limbal stem cell deficiency. Transplantation, 72(9), 1478–85.PubMedGoogle Scholar
  78. 78.
    Pellegrini, G., Traverso, C. E., Franzi, A. T., Zingirian, M., Cancedda, R., & Luca, M. D. (1997). Long-term restoration of damaged corneal surfaces with autologous cultivated corneal epithelium. Lancet, 349(9057), 990–3.PubMedGoogle Scholar
  79. 79.
    Schwab, I. R. (1999). Cultured corneal epithelia for ocular surface disease. Trans Am Ophthalmol Soc, 97, 891–986.PubMedGoogle Scholar
  80. 80.
    Kenyon, K. R., & Tseng, S. C. (1989). Limbal autograft transplantation for ocular surface disorders. Ophthalmology, 96(5), 709–22.PubMedGoogle Scholar
  81. 81.
    Jenkins, C., Tuft, S., Liu, C., & Buckley, R. (1993). Limbal transplantation in the management of chronic contact-lens-associated epitheliopathy. Eye, 7, 629–33.PubMedGoogle Scholar
  82. 82.
    Tsubota, K., Satake, Y., Kaido, M., et al. (1999). Treatment of severe ocular-surface disorders with corneal epithelial stem-cell transplantation. N Engl J Med, 340(22), 1697–703.PubMedGoogle Scholar
  83. 83.
    Tseng, S. C. G., Prabhasawat, P., Barton, K., Gray, T., & Meller, D. (1998). Amniotic membrane transplantation with or without limbal allografts for corneal surface reconstruction in patients with limbal stem cell deficiency. Arch Ophthalmol, 116(4), 431–41.PubMedGoogle Scholar
  84. 84.
    Kim, J. C., & Tseng, S. C. G. (1995). Transplantation of preserved human amniotic membrane for surface reconstruction in severely damaged rabbit corneas. Cornea, 14(5), 473–84.PubMedGoogle Scholar
  85. 85.
    Stoiber, J., Muss, W. H., Pohla-Gubo, G., Ruckhofer, J., & Grabner, G. (2002). Histopathology of human corneas after amniotic membrane and limbal stem cell transplantation for severe chemical burn. Cornea, 21(5), 482–9.PubMedGoogle Scholar
  86. 86.
    Gris, O., del Campo, Z., Wolley-Dod, C., et al. (2002). Amniotic membrane implantation as a therapeutic contact lens for the treatment of epithelial disorders. Cornea, 21(1), 22–7.PubMedGoogle Scholar
  87. 87.
    Rama, P., Matuska, S., Paganoni, G., Spinelli, A., De Luca, M., & Pellegrini, G. (2010). Limbal stem-cell therapy and long-term corneal regeneration. N Engl J Med, 363(2), 147–55.PubMedGoogle Scholar
  88. 88.
    Shortt, A. J., Tuft, S. J., & Daniels, J. T. (2010). Ex vivo cultured limbal epithelial transplantation. A clinical perspective. Ocul Surf, 8(2), 80–90.PubMedGoogle Scholar
  89. 89.
    Boneva, R. S., Folks, T. M., & Chapman, L. E. (2001). Infectious disease issues in xenotransplantation. Clin Microbiol Rev, 14(1), 1–14.PubMedGoogle Scholar
  90. 90.
    Manuelidis, E. E., Angelo, J. N., Gorgacz, E. J., Kim, J. H., & Manuelidis, L. (1977). Experimental creutzfeldt-jakob disease transmitted via the eye with infected cornea. N Engl J Med, 296(23), 1334–6.PubMedGoogle Scholar
  91. 91.
    Ahmad, S., Kolli, S., Lako, M., Figueiredo, F., & Daniels, J. T. (2010). Stem cell therapies for ocular surface disease. Drug Discov Today, 15(7–8), 306–13.PubMedGoogle Scholar
  92. 92.
    Green, H. (2008). The birth of therapy with cultured cells. Bioessays, 30(9), 897–903.PubMedGoogle Scholar
  93. 93.
    Di Girolamo, N., Chui, J., Wakefield, D., & Coroneo, M. T. (2007). Cultured human ocular surface epithelium on therapeutic contact lenses. Br J Ophthalmol, 91(4), 459–64.PubMedGoogle Scholar
  94. 94.
    Deshpande, P., Notara, M., Bullett, N., Daniels, J. T., Haddow, D. B., & MacNeil, S. (2009). Development of a surface-modified contact lens for the transfer of cultured limbal epithelial cells to the cornea for ocular surface diseases. Tissue Eng Part A, 15(10), 2889–902.PubMedGoogle Scholar
  95. 95.
    Pino, C. J., Haselton, F. R., & Chang, M. S. (2005). Seeding of corneal wounds by epithelial cell transfer from micropatterned PDMS contact lenses. Cell Transplant, 14(8), 565–71.PubMedGoogle Scholar
  96. 96.
    Shapiro, M., Friend, J., & Thoft, R. (1981). Corneal re-epithelialization from the conjunctiva. Invest Ophthalmol Vis Sci, 21(1), 135–42.PubMedGoogle Scholar
  97. 97.
    Tanioka, H., Kawasaki, S., Yamasaki, K., et al. (2006). Establishment of a cultivated human conjunctival epithelium as an alternative tissue source for autologous corneal epithelial transplantation. Invest Ophthalmol Vis Sci, 47(9), 3820–7.PubMedGoogle Scholar
  98. 98.
    Ang, L. P. K., Tanioka, H., Kawasaki, S., et al. (2010). Cultivated human conjunctival epithelial transplantation for total limbal stem cell deficiency. Invest Ophthalmol Vis Sci, 51(2), 758–64.PubMedGoogle Scholar
  99. 99.
    Sun, T. T., & Green, H. (1977). Cultured epithelial cells of cornea, conjunctiva and skin: absence of marked intrinsic divergence of their differentiated states. Nature, 269(5628), 489–93.PubMedGoogle Scholar
  100. 100.
    Ferrari, S., Barbaro, V., Di Iorio, E., Fasolo, A., & Ponzin, D. (2009). Advances in corneal surgery and cell therapy: challenges and perspectives for the eye banks. Expert Rev Ophthalmol, 4, 317–29.Google Scholar
  101. 101.
    Cauchi, P. A., Ang, G. S., Azuara-Blanco, A., & Burr, J. M. (2008). A systematic literature review of surgical interventions for limbal stem cell deficiency in humans. Am J Ophthalmol, 146(2), 251–9.PubMedGoogle Scholar
  102. 102.
    Miri, A., Mathew, M., & Dua, H. S. (2010). Quality of life after limbal transplants. Ophthalmology, 117(3), 638.PubMedGoogle Scholar
  103. 103.
    Reinhard, T., Spelsberg, H., Henke, L., et al. (2004). Long-term results of allogeneic penetrating limbo-keratoplasty in total limbal stem cell deficiency. Ophthalmology, 111(4), 775–82.PubMedGoogle Scholar
  104. 104.
    Daya, S. M., Watson, A., Sharpe, J. R., et al. (2005). Outcomes and DNA analysis of ex vivo expanded stem cell allograft for ocular surface reconstruction. Ophthalmology, 112(3), 470–7.PubMedGoogle Scholar
  105. 105.
    Pauklin, M., Fuchsluger, T. A., Westekemper, H., Steuhl, K. P., & Meller, D. (2010). Midterm results of cultivated autologous and allogeneic limbal epithelial transplantation in limbal stem cell deficiency. Dev Ophthalmol, 45, 57–70.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Inflammation and Infection Research Centre, Department of Pathology, School of Medical SciencesUniversity of New South WalesSydneyAustralia

Personalised recommendations