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Review

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

by
Emily Elizabeth Fresenko
1,2,
Jian-Xing Ma
3,
Matthew Giegengack
4,
Atalie Carina Thompson
4,
Anthony Atala
1,
Andrew J. W. Huang
5 and
Yuanyuan Zhang
1,*
1
Wake Forest Institute for Regenerative Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC 27101, USA
2
School of Medicine, Wake Forest University, Winston-Salem, NC 27101, USA
3
Department of Biochemistry, School of Medicine, Wake Forest University, Winston-Salem, NC 27101, USA
4
Department of Ophthalmology, School of Medicine, Wake Forest University, Winston-Salem, NC 27101, USA
5
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(15), 7501; https://doi.org/10.3390/ijms26157501 (registering DOI)
Submission received: 1 July 2025 / Revised: 28 July 2025 / Accepted: 1 August 2025 / Published: 3 August 2025
(This article belongs to the Special Issue Enhancing Stem Cell Grafting in Tissue Regeneration and Repair)

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.
Keywords: corneal reconstruction; stem cells; epithelium; barrier function; regenerative medicine corneal reconstruction; stem cells; epithelium; barrier function; regenerative medicine

Share and Cite

MDPI and ACS Style

Fresenko, E.E.; Ma, J.-X.; Giegengack, M.; Thompson, A.C.; Atala, A.; Huang, A.J.W.; Zhang, Y. Stem Cell-Derived Corneal Epithelium: Engineering Barrier Function for Ocular Surface Repair. Int. J. Mol. Sci. 2025, 26, 7501. https://doi.org/10.3390/ijms26157501

AMA Style

Fresenko EE, Ma J-X, Giegengack M, Thompson AC, Atala A, Huang AJW, Zhang Y. Stem Cell-Derived Corneal Epithelium: Engineering Barrier Function for Ocular Surface Repair. International Journal of Molecular Sciences. 2025; 26(15):7501. https://doi.org/10.3390/ijms26157501

Chicago/Turabian Style

Fresenko, Emily Elizabeth, Jian-Xing Ma, Matthew Giegengack, Atalie Carina Thompson, Anthony Atala, Andrew J. W. Huang, and Yuanyuan Zhang. 2025. "Stem Cell-Derived Corneal Epithelium: Engineering Barrier Function for Ocular Surface Repair" International Journal of Molecular Sciences 26, no. 15: 7501. https://doi.org/10.3390/ijms26157501

APA Style

Fresenko, E. E., Ma, J.-X., Giegengack, M., Thompson, A. C., Atala, A., Huang, A. J. W., & Zhang, Y. (2025). Stem Cell-Derived Corneal Epithelium: Engineering Barrier Function for Ocular Surface Repair. International Journal of Molecular Sciences, 26(15), 7501. https://doi.org/10.3390/ijms26157501

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