Feasibility Study of Human Corneal Endothelial Cell Transplantation Using an In Vitro Human Corneal Model

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. Materials and Methods: A CE decompensation model was established by removal of the DM/Endothelium complex from human cadaveric corneas in an air-interface organ culture system (Group 2) and compared to 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 corneal endothelial cells (hCECs) in Group 4 corneas. Functional effects on stromal thickness were undertaken with histological analysis 3-10 days post-cell therapy treatment. Results: Removal of the DM/Endothelium complex in Group 2 corneas resulted in a stromal thickness of 903 ± 86 μm at 12 hours in comparison to 557 ± 72 μm in Group 1 corneas. The stromal thickness reduced from 1218 ± 153 μm to 458 ± 90 μm (63 ± 6 %, p=0.001) post cell transplantation in Group 3) and from 1100 ± 86 μm to 489 ± 94 μm (55 ± 7 %, p=0.00004 in Group 4 respectively. Post-transplantation histology demonstrated the formation of a monolayer of corneal endothelium attached to the posterior stromal surface. Conclusion: Direct transplantation of cultured hCECs and immortalized HCEC-12 to bare posterior corneal stroma resulted in the formation of an endothelial monolayer and restoration of stromal hydration to physiological thickness, demonstrating the feasibility of cell therapy in the treatment of corneal endothelial decompensation in a human in vitro model