Effect of Topical application of Lyophilized Xenogenous Mesenchymal Stem Cell-Derived Extracellular Vesicles on Central and Peripheral Corneal Ulcers Healing in Rabbits

Citation:
Bahr, M. M., M. Samer, K. Abo-EL-Sooud, S. M. Kamel, M. A. Fouly, A. N. Abdallah, A. A. Shamaa, and O. S. el-Tookhy, "Effect of Topical application of Lyophilized Xenogenous Mesenchymal Stem Cell-Derived Extracellular Vesicles on Central and Peripheral Corneal Ulcers Healing in Rabbits", Advances in Animal and Veterinary Sciences, vol. 11, no. 1: ResearchersLinks Ltd, pp. 132 – 140, 2023.

Abstract:

Background: Corneal ulcer is the discontinuation of the surface epithelial layer of the cornea with variable amounts of the stroma affected. Recent research suggests that Extracellular Vesicles (EVs) of stem cells have the same effects on target cells that their parental stem cells act, these effects are brought on by paracrine signaling involves the release of cytokines and nucleic acids (DNA, mRNA, and miRNA) which may lead to alteration of the gene expression, proliferation, and differentiation of the recipient cells. Methodology: 24 male New Zealand albino rabbits were used in this study, divided randomly into 4 groups (6 rabbits per group), induction of corneal ulcers centrally in groups (I, II) and peripherally in (III, IV). Treated groups are (I, III) using topical lyophilized canine Mesenchymal Stem Cells derived EVs & control groups are (II, IV) using topical normal saline. Result: both treated groups appeared fluorescein negative at the 5th day and are characterized by rapid reepithelization significantly earlier than control groups which were still fluorescein positive. AS-OCT (Anterior Segment Optical Coherence Tomography) showed well-healed epithelium with intact and homogenous stroma on the 5th day in both treated groups, but control groups showed irregular arrangements of epithelial plaques and presented some abnormalities as stromal fibrosis and sub-epithelial cyst formation. Histopathology in both treated groups showed the development of a complete layer of epithelium within 1week which increased in rows at 2nd and 3rd weeks of treatment and the stromal edema decreased with time unlike control groups that showed weak fragmented epithelium development, sub-epithelial hemorrhage and vascularization. These findings prove that EVs have the ability to heal corneal wounds even if in the peripheral parts of the cornea that are deficient in limbal stem cells. Conclusion: In terms of safety, quality, regulatory concerns, and cost, EVs are superior to corneal transplantation and live stem cell therapy. © 2023 by the authors. Licensee ResearchersLinks Ltd, England, UK. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons. org/licenses/by/4.0/).

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