Clinical Trials of Limbal Stem Cell Deficiency Treated with Oral Mucosal Epithelial Cells

Abstract

The corneal surface is an essential organ necessary for vision, and its clarity must be maintained. The corneal epithelium is renewed by limbal stem cells, located in the limbus and in palisades of Vogt. Palisades of Vogt maintain the clearness of the corneal epithelium by blocking the growth of conjunctival epithelium and the invasion of blood vessels over the cornea. The limbal region can be damaged by chemical burns, physical damage (e.g., by contact lenses), congenital disease, chronic inflammation, or limbal surgeries. The degree of limbus damage is associated with the degree of limbal stem cells deficiency (partial or total). For a long time, the only treatment to restore vision was grafting part of the healthy cornea from the other eye of the patient or by transplanting a cornea from cadavers. The regenerative medicine and stem cell therapies have been applied to restore normal vision using different methodologies. The source of stem cells varies from embryonic stem cells, mesenchymal stem cells, to induced pluripotent stem cells. This review focuses on the use of oral mucosa epithelial stem cells and their use in engineering cell sheets to treat limbal stem cell deficient patients.

A Scarless Healing Tale: Comparing Homeostasis and Wound Healing of Oral Mucosa With Skin and Oesophagus

“…Tissue-engineered cell sheets of autologous oral epithelial cells alone, or combined with other tissues have been used for ocular diseases treatment, including eyelid and corneal reconstructions ( Nishida et al, 2004 ; Yoshizawa et al, 2004 ; Oliva et al, 2020 ; Sasaki et al, 2020 ). Using an in vivo rabbit model of total limbal SC deficiency, dental pulp SCs were used in a tissue-engineered cell sheet for ocular surface reconstruction ( Gomes et al, 2010 ) highlighting the plasticity of these cells.…”

Development of Multilayer Mesenchymal Stem Cell Cell Sheets

“…Even if federal agencies do not have specific guidelines for the follow-up and biodistribution on patients after cell transplantation, they strongly recommend a long-term follow-up during the animal preclinical studies (based on the animal lifespan) to determine if there is a risk or not for the patients during the clinical trials. For example, for transplantation of corneal-like cell sheets on patients with limbal stem cell deficiency, the average time of follow-up was 2 years, with a maximum of 7.5 years [113,114]. Different methodologies were developed to study cell migration and location, after their transplantation (Table 1).…”

The progress in corneal translational medicine

“…The first treatment developed to reverse LSCD was transplantation. 240 For patients with unilateral limbal stem cell deficiency, three different methodologies are available. The first involves transferring a large limbal graft from the healthy eye to the LSCD eye.…”