Differentiation and molecular profiling of human embryonic stem cell-derived corneal epithelial cells
J Brzeszczynska1, K Samuel2, S Greenhough3
1Tissue Injury and Repair Group, MRC Centre for Regenerative Medicine, Chancellor's Building, University of Edinburgh, Edinburgh EH16 4SB, Scotland, UK.
Abstract:
It has been suggested that the isolation of scalable populations of limbal stem cells may lead to radical changes in ocular therapy. In particular, the derivation and transplantation of corneal stem cells from these populations may result in therapies providing clinical normality of the diseased or damaged cornea. Although feasible in theory, the lack of donor material in sufficient quantity and quality currently limits such a strategy. A potential scalable source of corneal cells could be derived from pluripotent stem cells (PSCs). We developed an in vitro and serum-free corneal differentiation model which displays significant promise. Our stepwise differentiation model was designed with reference to development and gave rise to cells which displayed similarities to epithelial progenitor cells which can be specified to cells displaying a corneal epithelial phenotype. We believe our approach is novel, provides a robust model of human development and in the future, may facilitate the generation of corneal epithelial cells that are suitable for clinical use. Additionally, we demonstrate that following continued cell culture, stem cell-derived corneal epithelial cells undergo transdifferentiation and exhibit squamous metaplasia and therefore, also offer an in vitro model of disease.
Insights
Generating corneal epithelial cells from pluripotent stem cells (PSCs) offers a promising scalable source for ocular therapy. This novel serum-free model may lead to clinical treatments for damaged corneas and disease modeling.
Area of Science:
- Ophthalmology
- Stem Cell Biology
- Regenerative Medicine
Background:
- Limbal stem cell isolation is crucial for ocular therapy but limited by donor material.
- Pluripotent stem cells (PSCs) present a potential scalable source for corneal cells.
- Current strategies for corneal repair face limitations in cell availability and quality.
Purpose of the Study:
- To develop a scalable, in vitro, serum-free model for corneal epithelial cell differentiation from PSCs.
- To investigate the potential of PSCs as a source for clinical applications in treating corneal diseases.
- To establish an in vitro model for studying corneal diseases like squamous metaplasia.
Main Methods:
- Developed a stepwise, serum-free in vitro differentiation model for corneal cells.
- Utilized pluripotent stem cells (PSCs) as the starting material.
- Analyzed cell phenotypes and differentiation pathways, including transdifferentiation and metaplasia.
Main Results:
- Successfully generated cells with characteristics of corneal epithelial progenitor cells.
- Achieved differentiation into cells displaying a corneal epithelial phenotype.
- Observed transdifferentiation and squamous metaplasia in cultured stem cell-derived corneal epithelial cells.
Conclusions:
- The developed model shows promise for generating clinically suitable corneal epithelial cells from PSCs.
- This approach offers a novel and robust model of human corneal development.
- The model facilitates in vitro study of corneal diseases, including squamous metaplasia.
