Review

.2016:2016:9798374.

doi: 10.1155/2016/9798374. Epub 2015 Dec 14.

Limbal Stem Cell Deficiency: Current Treatment Options and Emerging Therapies

Michel Haagdorens¹, Sara Ilse Van Acker², Veerle Van Gerwen², Sorcha Ní Dhubhghaill³, Carina Koppen³, Marie-José Tassignon³, Nadia Zakaria⁴

Affiliations

¹ Faculty of Medicine and Health Sciences, Department of Ophthalmology, Visual Optics and Visual Rehabilitation, University of Antwerp, Campus Drie Eiken, T building, T4-Ophthalmology, Universiteitsplein 1, 2610 Antwerp, Belgium; Department of Ophthalmology, Antwerp University Hospital, Dienst Oogheelkunde, Wilrijkstraat 10, 2650 Edegem, Belgium; Research Foundation-Flanders, Egmontstraat 5, 1000 Brussels, Belgium.
² Faculty of Medicine and Health Sciences, Department of Ophthalmology, Visual Optics and Visual Rehabilitation, University of Antwerp, Campus Drie Eiken, T building, T4-Ophthalmology, Universiteitsplein 1, 2610 Antwerp, Belgium.
³ Faculty of Medicine and Health Sciences, Department of Ophthalmology, Visual Optics and Visual Rehabilitation, University of Antwerp, Campus Drie Eiken, T building, T4-Ophthalmology, Universiteitsplein 1, 2610 Antwerp, Belgium; Department of Ophthalmology, Antwerp University Hospital, Dienst Oogheelkunde, Wilrijkstraat 10, 2650 Edegem, Belgium.
⁴ Faculty of Medicine and Health Sciences, Department of Ophthalmology, Visual Optics and Visual Rehabilitation, University of Antwerp, Campus Drie Eiken, T building, T4-Ophthalmology, Universiteitsplein 1, 2610 Antwerp, Belgium; Department of Ophthalmology, Antwerp University Hospital, Dienst Oogheelkunde, Wilrijkstraat 10, 2650 Edegem, Belgium; Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, CCRG-Oogheelkunde, Wilrijkstraat 10, 2650 Edegem, Belgium.

PMID:26788074
PMCID: PMC4691643
DOI: 10.1155/2016/9798374

Review

Limbal Stem Cell Deficiency: Current Treatment Options and Emerging Therapies

Michel Haagdorens et al. Stem Cells Int.2016.

.2016:2016:9798374.

doi: 10.1155/2016/9798374. Epub 2015 Dec 14.

Authors

Michel Haagdorens¹, Sara Ilse Van Acker², Veerle Van Gerwen², Sorcha Ní Dhubhghaill³, Carina Koppen³, Marie-José Tassignon³, Nadia Zakaria⁴

Affiliations

¹ Faculty of Medicine and Health Sciences, Department of Ophthalmology, Visual Optics and Visual Rehabilitation, University of Antwerp, Campus Drie Eiken, T building, T4-Ophthalmology, Universiteitsplein 1, 2610 Antwerp, Belgium; Department of Ophthalmology, Antwerp University Hospital, Dienst Oogheelkunde, Wilrijkstraat 10, 2650 Edegem, Belgium; Research Foundation-Flanders, Egmontstraat 5, 1000 Brussels, Belgium.
² Faculty of Medicine and Health Sciences, Department of Ophthalmology, Visual Optics and Visual Rehabilitation, University of Antwerp, Campus Drie Eiken, T building, T4-Ophthalmology, Universiteitsplein 1, 2610 Antwerp, Belgium.
³ Faculty of Medicine and Health Sciences, Department of Ophthalmology, Visual Optics and Visual Rehabilitation, University of Antwerp, Campus Drie Eiken, T building, T4-Ophthalmology, Universiteitsplein 1, 2610 Antwerp, Belgium; Department of Ophthalmology, Antwerp University Hospital, Dienst Oogheelkunde, Wilrijkstraat 10, 2650 Edegem, Belgium.
⁴ Faculty of Medicine and Health Sciences, Department of Ophthalmology, Visual Optics and Visual Rehabilitation, University of Antwerp, Campus Drie Eiken, T building, T4-Ophthalmology, Universiteitsplein 1, 2610 Antwerp, Belgium; Department of Ophthalmology, Antwerp University Hospital, Dienst Oogheelkunde, Wilrijkstraat 10, 2650 Edegem, Belgium; Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, CCRG-Oogheelkunde, Wilrijkstraat 10, 2650 Edegem, Belgium.

PMID:26788074
PMCID: PMC4691643
DOI: 10.1155/2016/9798374

Abstract

Severe ocular surface disease can result in limbal stem cell deficiency (LSCD), a condition leading to decreased visual acuity, photophobia, and ocular pain. To restore the ocular surface in advanced stem cell deficient corneas, an autologous or allogenic limbal stem cell transplantation is performed. In recent years, the risk of secondary LSCD due to removal of large limbal grafts has been significantly reduced by the optimization of cultivated limbal epithelial transplantation (CLET). Despite the great successes of CLET, there still is room for improvement as overall success rate is 70% and visual acuity often remains suboptimal after successful transplantation. Simple limbal epithelial transplantation reports higher success rates but has not been performed in as many patients yet. This review focuses on limbal epithelial stem cells and the pathophysiology of LSCD. State-of-the-art therapeutic management of LSCD is described, and new and evolving techniques in ocular surface regeneration are being discussed, in particular, advantages and disadvantages of alternative cell scaffolds and cell sources for cell based ocular surface reconstruction.

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Figures

**Figure 1**
(A) Overview of the anterior surface of the human eye, in which the sclera (with overlying conjunctiva) and cornea can easily be discriminated. (B) The limbus is highly pigmented in some individuals, and allows clear visualization of the limbal palisades of Vogt. The cornea (and underlying dark iris) is pictured above, and conjunctiva (and underlying sclera) below. (C) Diagram of a cross section through the conjunctival, limbal and corneal epithelium. Limbal progenitor cells (a) differentiate into transient amplifying cells (b), post-mitotic cells (c) and finally terminally differentiated cells (d). Movement of cells in X, Y, Z direction is presented by proliferation of stem cells(a), differentiation and centripetal migration (b, c), and desquamation (d) respectively.

**Figure 2**
Haematoxylin staining of cross section through normal limbal region. Arrow in (a) indicates a LESC containing limbal epithelial crypt; arrowheads indicate blood vessels. Arrow in (b) indicates a limbal crypt, flanked by two focal stromal projections (arrowhead).

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References

1. McTigue J. W. The human cornea: a light and electron microscopic study of the normal cornea and its alterations in various dystrophies. Transactions of the American Ophthalmological Society. 1967;65:591–660. - PMC - PubMed
1. Cotsarelis G., Cheng S.-Z., Dong G., Sun T.-T., Lavker R. M. Existence of slow-cycling limbal epithelial basal cells that can be preferentially stimulated to proliferate: implications on epithelial stem cells. Cell. 1989;57(2):201–209. doi: 10.1016/0092-8674(89)90958-6. - DOI - PubMed
1. Hall P. A., Watt F. M. Stem cells: the generation and maintenance of cellular diversity. Development. 1989;106(4):619–633. - PubMed
1. Schermer A., Galvin S., Sun T. T. Differentiation-related expression of a major 64K corneal keratin in vivo and in culture suggests limbal location of corneal epithelial stem cells. The Journal of Cell Biology. 1986;103(1):49–62. doi: 10.1083/jcb.103.1.49. - DOI - PMC - PubMed
1. Shapiro M. S., Friend J., Thoft R. A. Corneal re-epithelialization from the conjunctiva. Investigative Ophthalmology & Visual Science. 1981;21(1, part 1):135–142. - PubMed

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Limbal Stem Cell Deficiency: Current Treatment Options and Emerging Therapies

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Limbal Stem Cell Deficiency: Current Treatment Options and Emerging Therapies

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