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干细胞衍生的角膜上皮:用于眼表修复的屏障功能工程

Stem Cell-Derived Corneal Epithelium: Engineering Barrier Function for Ocular Surface Repair.

作者信息

Fresenko Emily Elizabeth, Ma Jian-Xing, Giegengack Matthew, Thompson Atalie Carina, Atala Anthony, Huang Andrew J W, Zhang Yuanyuan

机构信息

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.

出版信息

Int J Mol Sci. 2025 Aug 3;26(15):7501. doi: 10.3390/ijms26157501.


DOI:10.3390/ijms26157501
PMID:40806627
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12347428/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a94f/12347428/a27b285a27d1/ijms-26-07501-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a94f/12347428/ce4c456981f5/ijms-26-07501-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a94f/12347428/3315f30f7050/ijms-26-07501-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a94f/12347428/a27b285a27d1/ijms-26-07501-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a94f/12347428/ce4c456981f5/ijms-26-07501-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a94f/12347428/3315f30f7050/ijms-26-07501-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a94f/12347428/a27b285a27d1/ijms-26-07501-g003.jpg

相似文献

[1]
Stem Cell-Derived Corneal Epithelium: Engineering Barrier Function for Ocular Surface Repair.

Int J Mol Sci. 2025-8-3

[2]
Deep anterior lamellar keratoplasty versus penetrating keratoplasty for treating keratoconus.

Cochrane Database Syst Rev. 2014-7-22

[3]
Case Report: Simultaneous penetrating keratoplasty with autologous simple limbal epithelial transplantation as an alternative to keratoprosthesis.

F1000Res. 2023

[4]
Advances in Regenerative Medicine, Cell Therapy, and 3D Bioprinting for Corneal, Oculoplastic, and Orbital Surgery.

Adv Exp Med Biol. 2025-3-26

[5]
Nocardia Keratitis

2025-1

[6]
Endothelial keratoplasty versus penetrating keratoplasty for Fuchs endothelial dystrophy.

Cochrane Database Syst Rev. 2014-2-14

[7]
Autologous Glueless Simple Limbal Epithelial Transplantation for Unilateral Stem Cell Deficiency Using Femtosecond Laser-Assisted Limbal Stem Cell Harvesting: The Report of the First 3 Clinical Cases.

Cornea. 2025-2-21

[8]
Descemet's membrane endothelial keratoplasty (DMEK) versus Descemet's stripping automated endothelial keratoplasty (DSAEK) for corneal endothelial failure.

Cochrane Database Syst Rev. 2018-6-25

[9]
Endothelial keratoplasty versus penetrating keratoplasty for Fuchs endothelial dystrophy.

Cochrane Database Syst Rev. 2011-7-6

[10]
Immunosuppressants for the prophylaxis of corneal graft rejection after penetrating keratoplasty.

Cochrane Database Syst Rev. 2015-8-27

本文引用的文献

[1]
Autologous glueless simple oral mucosal transplantation for the repair of limbal stem cell deficiency ocular surface in a rabbit model.

Sci Rep. 2025-3-29

[2]
Cultivated autologous limbal epithelial cell (CALEC) transplantation for limbal tem cell deficiency: a phase I/II clinical trial of the first xenobiotic-free, serum-free, antibiotic-free manufacturing protocol developed in the US.

Nat Commun. 2025-3-4

[3]
Corneal Treatment, Repair, and Regeneration: Exosomes at Rescue.

Pharmaceutics. 2024-11-7

[4]
Induced pluripotent stem-cell-derived corneal epithelium for transplant surgery: a single-arm, open-label, first-in-human interventional study in Japan.

Lancet. 2024-11-16

[5]
Molecular and Cellular Mechanisms of the Therapeutic Effect of Mesenchymal Stem Cells and Extracellular Vesicles in Corneal Regeneration.

Int J Mol Sci. 2024-10-16

[6]
Innovative Bioscaffolds in Stem Cell and Regenerative Therapies for Corneal Pathologies.

Bioengineering (Basel). 2024-8-23

[7]
Aquaporins in the Cornea.

Int J Mol Sci. 2024-3-28

[8]
Focus on limbal stem cell deficiency and limbal cell transplantation.

World J Transplant. 2023-12-18

[9]
Protocol for isolating human BCAM-positive corneal progenitor cells by flow cytometry and cell sorting.

STAR Protoc. 2023-9-15

[10]
Corneal regeneration strategies: From stem cell therapy to tissue engineered stem cell scaffolds.

Biomed Pharmacother. 2023-9

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