Abstract
Purpose :
Ocular surface disease pose a significant clinical challenge, with limited treatment options available. A cell therapy using conjunctival organoid–derived cell sheets offers a promising approach for conjunctival regeneration. We evaluate the safety and efficacy of conjunctival organoid–derived cell sheets in repairing conjunctival defects in a pre-clinical rabbit model.
Methods :
Human conjunctival organoids were established from small conjunctival biopsies (~1 mm2, N=6), recapitulating key features of the conjunctival epithelium, including an abundance of goblet cells. The organoids were then dissociated and seeded as single cells on a fibrin scaffold. A conjunctival defect was induced in immunosuppressed rabbits (N=34) by conjunctival excision (5.0 mm), followed by transplantation of the cell sheets (6.0 mm) onto the denuded area. Examinations were performed on postoperative days (POD) 7, 14, and 21 to assess conjunctival defects and wound healing. Immunohistological analysis was conducted on POD 7 and 21 to evaluate the regenerative capacity of the transplanted cells in more detail.
Results :
Eye examinations showed no signs of conjunctival defects or adverse effects on POD 7, 14, and 21. Histological examination revealed complete conjunctival regeneration with normal morphology and organization on POD 7 and 21. A regular distribution of mucin-producing goblet cells was observed in the fornix (18 cells/mm) and bulbar (9 cells/mm) conjunctiva. Mild infiltration of inflammatory cells in the episcleral and conjunctiva was observed on POD 7 and 21. Expression of human-specific CK14 on POD 7 (100%) and 14 (75%) indicated that transplanted cells specifically repopulated the defect, not the neighboring rabbit conjunctiva.
Conclusions :
Conjunctival organoid–derived cell sheets demonstrate promise for repairing conjunctival defects, offering a potential therapeutic strategy for ocular surface disorders.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.