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Feasibility Study of Human Corneal Endothelial Cell Transplantation Using an In Vitro Human Corneal Model
Kostadin Rolev1, Dominic G OʼDonovan2, Peter Coussons1
1Department of Biomedical and Forensic Sciences and the Vision & Eye Research Unit Cambridge, Anglia Ruskin University, Cambridgeshire, United Kingdom. Dr. Rolev is now with the Department of Bioengineering, Imperial College London, Royal School of Mines, South Kensington, London, United Kingdom.
Insights
Cell therapy using cultured human corneal endothelial cells effectively restored corneal hydration and thickness in an in vitro model of corneal decompensation. This demonstrates a feasible treatment approach for corneal endothelial disorders.
Area of Science:
- Ophthalmology
- Regenerative Medicine
- Cell Biology
Background:
- Corneal endothelial (CE) disorders can lead to corneal decompensation and vision loss.
- Current treatments often involve corneal transplantation, which has limitations.
- Cell therapy offers a potential alternative for treating CE disorders.
Purpose of the Study:
- To evaluate the feasibility of a cell therapy approach for corneal endothelial disorders.
- To utilize an in vitro model of human corneal decompensation to test cell transplantation.
Main Methods:
- A human corneal decompensation model was created by removing the Descemet membrane/endothelium complex.
- Cadaveric human corneas were cultured in an air interface system.
- Decompensated corneas were seeded with either immortalized human corneal endothelial cells (HCEC-12) or primary human CE cells.
- Stromal thickness was assessed via histological analysis after cell therapy.
Main Results:
- Decompensated corneas showed significant stromal thickening compared to normal corneas.
- Cell transplantation with both HCEC-12 and primary CE cells significantly reduced stromal thickness.
- Histology confirmed the formation of a corneal endothelial monolayer on the posterior stroma post-transplantation.
Conclusions:
- Direct transplantation of cultured human CE cells can restore corneal endothelial function.
- This approach successfully formed an endothelial monolayer and normalized stromal hydration in vitro.
- Cell therapy is a feasible treatment strategy for corneal endothelial decompensation.
Purpose:
To test the feasibility of a cell therapy approach to treat corneal endothelial (CE) disorders using an in vitro model of human corneal decompensation.
Methods:
A CE decompensation model was established by removal of the Descemet membrane/endothelium complex from cadaveric human corneas in an air interface organ culture system (group 2) and compared with normal corneas (group 1). The posterior stroma of decompensated corneas was seeded with immortalized human corneal endothelial cells (HCEC-12) in group 3 and passage 0 primary human CE cells in group 4 corneas. Functional effects on stromal thickness were determined with histological analysis 3 to 10 days after cell therapy treatment.
Results:
Removal of the Descemet membrane/endothelium complex in group 2 corneas resulted in a stromal thickness of 903 ± 86 μm at 12 hours compared with 557 ± 72 μm in group 1 corneas. Stromal thickness reduced from 1218 ± 153 μm to 458 ± 90 μm (63% ± 6%, P = 0.001) after cell transplantation in group 3 and from 1100 ± 86 μm to 489 ± 94 μm (55% ± 7%, P = 0.00004) in group 4. Posttransplantation histology demonstrated formation of a monolayer of corneal endothelium attached to the posterior stromal surface.
Conclusions:
Direct transplantation of cultured human CE cells and immortalized HCEC-12 to bare posterior corneal stroma resulted in formation of an endothelial monolayer and restoration of stromal hydration to physiological thickness, demonstrating the feasibility of cell therapy in treatment of CE decompensation in a human in vitro model.
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