Intrastromal Implantation Of Hipsc-Derived Neural Crest Cells For Corneal Stromal Regeneration And Improvement Of Established Corneal Scars In A Rabbit Model
Published 2026 - 44th Congress of the ESCRS
Reference: FP22.06 | Type: Free paper | DOI: 10.82333/38dm-gh18
Authors: Dr Hao Zhang* 1 , A/Prof. Jorge L. Alió 1 , Dr Alejandra E. Rodriguez 2 , Dr Marta Cadenas-Martin 3 , A/Prof. Maria P De Miguel 3 , A/Prof. Jorge L. Alió del Barrio 1
1Vissum Grupo Miranza,Alicante,Spain;Division of Ophthalmology,Universidad Miguel Hernández,Alicante,Spain, 2Vissum Grupo Miranza,Alicante,Spain, 3Cell Engineering Laboratory,La Paz University Hospital Health Research Institute, IdiPAZ,Madrid,Spain
Purpose
To evaluate the early safety and surgical feasibility of intrastromal implantation of human induced pluripotent stem cell–derived neural crest cells (hiPSC-NCCs) for corneal stromal regeneration, and to explore their therapeutic effect on established stromal scars in a rabbit model.
Setting
Laboratory-based animal study.
Methods
In 18 New Zealand White rabbits, three phases were performed: (1) biocompatibility—hiPSC-NCCs (1×106/50 µL PBS) injected into a mid-stromal pocket of normal corneas (n=6); (2) scar model—standardized stromal scar induced (3-mm trephination, 300-µm lamellar dissection, Algerbrush II polishing) and followed for 6 months by slit-lamp, AS-OCT, densitometry and IVCM (n=4); (3) therapy—hiPSC-NCC implantation 3 months after scar induction in scarred corneas (n=8) with 3-month follow-up. A dimensionless scar index was calculated from AS-OCT B-scans (ImageJ; normalized gray levels).
Results
Scar induction produced a reproducible haze stable for 6 months, with a hyper-reflective band on AS-OCT, increased densitometry and fibrotic features on IVCM. hiPSC-NCC implantation was technically feasible in all operated eyes. At 3 months, treated corneas (with or without pre-existing scars) regained slit-lamp transparency, with resolution of stromal deposits and collagen-like tissue occupying the pocket plane. No persistent epithelial defects, clinically significant neovascularization, intraocular inflammation, or immune-rejection signs were observed. The scar index was higher in untreated than treated scars (36 B-scans/4 eyes vs 36 B-scans/4 eyes: 1.86±0.18 vs 1.56±0.11; Welch’s t test, P=0.036).
Conclusions
Intrastromal implantation of hiPSC-NCCs in rabbit corneas is surgically feasible and shows a favorable early safety profile, with no severe ocular complications or overt immune rejection. hiPSC-NCC therapy improved established stromal scars within a stable, reproducible scar model, supporting its potential for corneal stromal regeneration and scar treatment.