Abstract

Corneal failure is a highly prevalent cause of blindness. One special cause of corneal failure occurs due to malfunction or destruction of the limbal stem cell niche, upon which the superficial cornea depends for homeostatic maintenance and wound healing. Failure of the limbal niche is referred to as limbal stem cell deficiency. As the corneal epithelial stem cell niche is easily accessible, limbal stem cell-based therapy and regenerative medicine applied to the ocular surface are among the most highly advanced forms of this novel approach to disease therapy. However, the challenges are still great, including the development of cell-based products and understanding how they work in the patient’s eye. Advances are being made at the molecular, cellular, and tissue levels to alter disease processes and to reduce or eliminate blindness. Efforts must be coordinated from the most basic research to the most clinically oriented projects so that cell-based therapies can become an integrated part of the therapeutic armamentarium to fight corneal blindness. We undoubtedly are progressing along the right path because cell-based therapy for eye diseases is one of the most successful examples of global regenerative medicine.

Highlights

  • Published: 16 September 2021Ophthalmology is among the first medical science branches that have benefited from stem cell-based therapy and regenerative medicine

  • Many facts can account for this success, such as easy accessibility to the stem cell niches; a relatively easy follow-up of the applied therapies; the fact that the eyes are paired, non-vital organs; and the immune-privileged nature of the intraocular tissues and cornea [1]

  • The ideal goal in the management of corneal blindness due to LSCD is to restore the architecture of the limbal niche so that new stem cells, coming from internal and/or external sources, can repopulate the niche and can replicate in a successful way such that the corneal epithelium can be regenerated with its original properties: transparency, uniformity, and self-renewing capacity

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Summary

Introduction

Ophthalmology is among the first medical science branches that have benefited from stem cell-based therapy and regenerative medicine. Of all of the potential stem cell niches in the visual system [1], those located at the ocular surface are the most accessible for study and extraction of the stem cells, and they can be repaired if they fail and produce disease. Epithelial stem cell transplantation to repair the corneal surface is the most widely used stem cell-based therapy in clinical medicine. The anterior segment of the eye is composed of the ocular surface, the anterior sclera, the corneal stroma and endothelium, the anterior and posterior chambers containing the aqueous humor, the anterior uvea composed of the iris and ciliary body, and the crystalline lens. The most well-known and documented stem cell niche is located at the limbus, where the transparent cornea transitions to the opaque sclera and is overlain by the conjunctiva. The goals and challenges that this therapy constitute are the topic of this review

The Past
The Present
Cultivated Limbal Epithelial Transplantation
Autologous Non-Limbal Epithelial Cell Transplantation
Allogeneic Non-Limbal Stem Cell-Based Transplantation
The Future
Selection
Preclinical Challenges
Analysis of the Corneal Epithelium after Stem Cell-Based Transplantation
The Need to Reconstruct the Limbal Stem Cell Niche
Alternative Routes of Delivering Stem Cell-Therapy
Other Potential Sources of Non-Limbal Cells
Regulatory Challenges
Findings
Conclusions
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