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直接口腔黏膜上皮移植提供干细胞并促进角膜伤口愈合,以治疗难治性持续性角膜上皮缺损。

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

机构信息

Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, 200011, China.

Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, 200011, China.

出版信息

Exp Eye Res. 2022 Feb;215:108934. doi: 10.1016/j.exer.2022.108934. Epub 2022 Jan 7.

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.

摘要

持续性角膜上皮缺损(PED)可导致不可逆性失明,严重影响患者的社会功能和生活质量。对于难治性 PED,如角膜缘干细胞缺乏(LSCD),在不响应标准治疗的情况下,干细胞治疗是一种理想的方法。口腔黏膜上皮(OME)富含基底中的干细胞,是一种很有前途的自体生物材料,与角膜上皮结构非常相似。在本实验中,未培养的自体大鼠 OME 被直接应用于碱烧伤角膜。临床评估和组织学分析表明,移植加速了愈合过程,表现出更快的再上皮化和更好的角膜上皮屏障形成。为了进一步研究治疗机制,将口腔上皮移植到体外去上皮化的角膜进行器官培养。可以观察到口腔上皮细胞能够迁移到角膜表面并形成光滑的复层上皮。免疫荧光染色结果表明,来源于 OME 的再形成上皮在一定程度上保持了干细胞特性,并向角膜上皮表型转化。角膜基质可能为口腔干细胞的转分化提供合适的微环境。因此,体内和体外实验均表明口腔上皮在治疗难治性 PED 中可能发挥积极作用。

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