Direct oral mucosal epithelial transplantation supplies stem cells and promotes corneal wound healing to treat refractory persistent corneal epithelial defects

https://doi.org/10.1016/j.exer.2022.108934Get rights and content

Highlights

OME is an ideal autologous biomaterial abundant with stem cells and resemble to corneal epithelial structures.

Autologous OME transplantation could promote the wound healing of the rat alkali-burn injured corneas.

The de-epithelialized corneas could achieve re-epithelialization with the transplanted OME grafts.

The re-formed epithelium by OME transplantation maintained stemness and transformed to corneal epithelial phenotype.

OME transplantation could be a simple and effective method for the treatment of persistent corneal epithelial defects.

Abstract

Persistent corneal epithelial defects (PED) can lead to irreversible blindness, seriously affecting the social function and life quality of these patients. When it comes to refractory PED, such as limbal stem cell deficiency (LSCD), that does not respond to standard managements, stem cell therapy is an ideal method. Oral mucosal epithelium (OME) abundant with stem cells within the base, is a promising autologous biomaterial, with much resemblance to corneal epithelial structures. In this experiment, uncultured autologous rat OME was directly applied to alkali burned corneas. Clinical evaluations and histological analyses showed that the transplantation accelerated the healing process, presenting faster re-epithelization and better formation of corneal epithelial barrier. To further investigate the therapeutic mechanism, oral epithelium was transplanted to de-epithelialized cornea in vitro for organ culture. It could be observed that the oral epithelial cells could migrate to the corneal surface and form smooth and stratified epithelium. Immunofluorescence staining results showed that the re-formed epithelium derived from OME, maintained stemness and transformed to corneal epithelial phenotype to some extent. Corneal stroma may provide the suitable microenvironment to promote the trans-differentiation of oral stem cells. Thus, both in vivo and in vitro experiments suggested that oral epithelium could play a positive role in treating refractory PED.

Keywords

Persistent corneal epithelial defects
Oral mucosal epithelial transplantation
Organ culture
Stem cell microenvironment
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Theses authors contributed equally to this work.

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