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Abstract
The cornea is critical for normal vision as it allows allowing light transmission to the retina. The corneal epithelium is renewed by limbal epithelial cells (LEC), which are located in the periphery of the cornea, the limbus. Damage or disease involving LEC may lead to various clinical presentations of limbal stem cell deficiency (LSCD). Both severe pain and blindness may result. Transplantation of cultured autologous oral mucosal epithelial cell sheet (CAOMECS) represents the first use of a cultured non-limbal autologous cell type to treat this disease. Among non-limbal cell types, CAOMECS and conjunctival epithelial cells are the only laboratory cultured cell sources that have been explored in humans. Thus far, the expression of p63 is the only predictor of clinical outcome following transplantation to correct LSCD. The optimal culture method and substrate for CAOMECS is not established. The present review focuses on cell culture methods, with particular emphasis on substrates. Most culture protocols for CAOMECS used amniotic membrane as a substrate and included the xenogeneic components fetal bovine serum and murine 3T3 fibroblasts. However, it has been demonstrated that tissue-engineered epithelial cell sheet grafts can be successfully fabricated using temperature-responsive culture surfaces and autologous serum. In the studies using different substrates for culture of CAOMECS, the quantitative expression of p63 was generally poorly reported; thus, more research is warranted with quantification of phenotypic data. Further research is required to develop a culture system for CAOMECS that mimics the natural environment of oral/limbal/corneal epithelial cells without the need for undefined foreign materials such as serum and feeder cells.
Highlights
Since 2003, nine cultured non-limbal cell sources have been successfully used to reconstruct the corneal epithelium in bilateral limbal stem cell deficiency (LSCD), in which limbal tissue is not recommended for harvest [8]
Among non-limbal cell types, cultured autologous oral mucosal epithelial cell sheet (CAOMECS) and conjunctival epithelial cells are the only laboratory cultured cell sources that have been explored in humans
The present review focuses on the current state of knowledge of the culture methods and substrates used for CAOMECS in ocular regeneration
Summary
The regenerating organs in the body (e.g., cornea, skin, and gut) harbor tissue-specific stem cells, which are responsible for tissue homeostasis and efficient healing in case of injury. The ocular surface is composed of corneal and conjunctival epithelium [1]. Numerous external factors and disorders (e.g., chemical or thermal injuries, microbial infections, surgeries involving the limbus, cicatricial pemphigoid, and aniridia) can lead to dysfunction or loss of limbal epithelial cells (LEC), resulting in either partial or total limbal stem cell deficiency (LSCD) [2]. The condition can be painful and may lead to reduced vision, or even blindness, by causing persistent epithelial defects, fibrovascular pannus, conjunctivalization, and superficial and deep vascularization of the cornea. The persistence of epithelial defects may result in ulceration, scarring, and corneal perforation [2].
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