Fresenko Emily Elizabeth, Ma Jian-Xing, Giegengack Matthew, Thompson Atalie Carina, Atala Anthony, Huang Andrew J W, Zhang Yuanyuan
Wake Forest Institute for Regenerative Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC 27101, USA.
School of Medicine, Wake Forest University, Winston-Salem, NC 27101, USA.
Int J Mol Sci. 2025 Aug 3;26(15):7501. doi: 10.3390/ijms26157501.
The cornea, the transparent anterior window of the eye, critically refracts light and protects intraocular structures. Corneal pathologies, including trauma, infection, chemical injury, metabolic diseases, genetic conditions, and age-related degeneration, can lead to significant visual impairment. While penetrating keratoplasty or full-thickness corneal transplantation remains a standard and effective intervention for severe corneal dysfunction, limitations in donor tissue availability and the risk of immunogenic graft rejection necessitate alternative therapeutic strategies. Furthermore, for cases of isolated epithelial disfunction, a full-thickness cornea graft may not be required or effective. This review examines the potential of corneal epithelial constructs derived from autologous stem cells with functional barrier properties for corneal reconstruction and in vitro pharmacotoxicity testing. In this review, we delineate the current limitations of corneal transplantation, the advantages of stem cell-based approaches, and recent advances in generating engineered corneal epithelium. Finally, we address remaining technical challenges and propose future research directions aimed at clinical translation.
角膜是眼睛前部的透明窗口,对光线进行关键的折射并保护眼内结构。角膜病变,包括创伤、感染、化学损伤、代谢疾病、遗传病症以及与年龄相关的退化,都可能导致严重的视力损害。虽然穿透性角膜移植术或全层角膜移植仍然是严重角膜功能障碍的标准且有效的干预措施,但供体组织可用性的限制以及免疫原性移植物排斥的风险使得需要替代治疗策略。此外,对于孤立的上皮功能障碍病例,可能不需要或无法有效进行全层角膜移植。本综述探讨了源自具有功能屏障特性的自体干细胞的角膜上皮构建体在角膜重建和体外药物毒性测试方面的潜力。在本综述中,我们阐述了角膜移植目前的局限性、基于干细胞方法的优势以及工程化角膜上皮生成的最新进展。最后,我们讨论了剩余的技术挑战,并提出了旨在临床转化的未来研究方向。
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