口腔粘膜上皮细胞移植（COMET）用于临床治疗双眼角膜缘干细胞衰竭已有10余年历史，最大的不足是移植后远期角膜血管化。口腔粘膜上皮细胞与角膜上皮细胞表型上的差异使得它不能从功能上完全替代角膜上皮。我们前期研究发现，niche细胞源exosomes（NC-Exos）可诱导口腔粘膜上皮干细胞（OMESCs）表达Pax6，并分化表达角膜上皮标志物K12和抗血管化物质sVEGFR-1，提示OMESCs诱导后具有功能性修复角膜上皮层的潜力。目前，诱导条件、治疗效果和诱导机制亟待进一步研究和探索。因此，本课题拟筛选NC-Exos诱导OMESCs的最优方案，研究诱导对OMESCs构建组织工程上皮层的抗血管化能力和屏障、防御、修复能力的影响，并进行动物实验验证其功能；通过筛选NC-Exos中特异表达的miRNA，深入研究其调控sVEGFR-1表达的机制。研究的成功有望解决COMET远期角膜血管化的难题。

Cultured oral mucosal epithelial transplantation(COMET) has been used as a treatment for bilateral limbal stem cell deficiency for more than ten years. The biggest drawback to COMET is corneal vascularization in long-term follow-ups. Oral mucosal epithelial cells cannot completely substitute and implement corneal epithelium’s function mainly because of its phenotypic differences from corneal epithelial cells. Our preliminary studies showed that niche cells derived exosomes (NC-Exos) could induce oral mucosal epithelial stem cells (OMESCs) to express Pax6, and to express the corneal epithelium marker--K12 and an anti-angiogenic factor--sVEGFR-1 when differentiating. These results indicate that the induced OMESCs have the potential to reconstruct the corneal epithelium functionally. Currently, it is urgent to study and investigate the inducing conditions, therapeutic effects, and mechanisms further. Considering that, we intend to select the best NC-Exos inducing conditions, to study how the induction would influence the anti-angiogenic, barrier, defending and repairing functions of tissue-engineered epithelium layers, and then to verify these functions by animal experiments. On the other hand, we will further investigate the sVEGFR-1 expression mechanism by screening the NC-Exos miRNA expression profiling and functional testing. The success of the study is expected to solve the problem of corneal vascularization after COMET in the long terms.