Abstract
Restoration of vision due to corneal blindness from corneal endothelial dysfunction can be achieved via a corneal transplantation. However, global shortage of donor tissues has driven the development cell-based therapeutics. With the capacity to propagate regulatory compliant human corneal endothelial cells (CEnCs), this study evaluated the functionality of propagated CEnCs delivered via tissue-engineered endothelial keratoplasty (TE-EK) or corneal endothelial cell injection (CE-CI) within a rabbit model of bullous keratopathy. For animals with TE-EK grafts, central corneal thickness (CCT) increased to >1000 μm post-operatively. Gradual thinning with improvements in corneal clarity was observed from week 1. CCT at week 3 was 484.3 ± 73.7 μm. In rabbits with CE-CI, corneal clarity was maintained throughout, and CCT at week 3 was 582.5 ± 171.5 μm. Control corneas remained significantly edematous throughout the study period compared to their respective experimental groups (p < 0.05). Characterization of excised corneas showed a monolayer with heterogeneously shaped CEnCs in both TE-EK and CE-CI groups. Immunohistochemistry demonstrated reactivity to anti-human specific nuclei antibody attributing corneal recovery to the functional human CEnCs. This study showed that regulatory compliant cell-based therapy for corneal endothelial dysfunction can be delivered by both TE-EK and CE-CI, and holds great promise as an alternative to traditional corneal transplantation.
Highlights
Www.nature.com/scientificreports primary corneal endothelial cells (CEnCs) have pushed the culture of these cells towards a regulatory compliant and well-defined system suitable for human clinical trials[27]
Building upon our previous report on the refinement of the dual media culture system for the propagation of functional primary human CEnCs towards regulatory compliance, we show in this study that the expanded CEnCs can be delivered into the AC via both the conventional tissue-engineered carrier-based ‘tissue engineered endothelial keratoplasty (TE-EK)’ approach as previously described[27], as well as by the cell-injection ‘cell injection (CE-CI)’ approach
We were www.nature.com/scientificreports able to show that CEnCs delivered by both approaches were able to reverse corneal blindness in a rabbit model of bullous keratopathy as shown by the recovery in corneal thickness in both treatment groups
Summary
Www.nature.com/scientificreports primary CEnCs have pushed the culture of these cells towards a regulatory compliant and well-defined system suitable for human clinical trials[27]. Complete functional recovery of the CE could not be clearly demonstrated following the injection of CEnCs in a feline model[33]; whereas studies reported by Okumura and colleagues showed complete functional recovery of the CE in both the rabbit[39] and non-human primate[40] models of bullous keratopathy It has since been reported, in a recently published clinical trial (UMIN000012534) that the injection of human CECs supplemented with ROCK inhibitor Y-27632 were able to repopulate and increase the CEC density of 11 patients with bullous keratopathy after 24 weeks[41], potentially strengthening the push for a cell-injection approach. The differences in functional recovery of the edematous rabbit corneas receiving the two different preparations of CEnCs via the two modes of delivery were evaluated
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