Reversed Corneal Fibroblasts Therapy Restores Transparency of Mouse Cornea after Injury

• Published in: International journal of molecular sciences Vol. 25; no. 13; p. 7053
• Main Authors: Surovtseva, Maria A, Krasner, Kristina Yu, Kim, Irina I, Surovtsev, Nikolay V, Chepeleva, Elena V, Bondarenko, Natalia A, Lykov, Alexander P, Bgatova, Nataliya P, Alshevskaya, Alina A, Trunov, Alexander N, Chernykh, Valery V, Poveshchenko, Olga V
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27-06-2024
• Subjects: Animals; cell therapy; Cell- and Tissue-Based Therapy - methods; Collagen; Cornea; Corneal Injuries - pathology; Corneal Injuries - therapy; Corneal Keratocytes; Corneal Stroma; corneal stromal scar; Disease Models, Animal; Edema; Extracellular matrix; Fibroblasts; Fibroblasts - metabolism; Homeostasis; Injuries; keratocytes; Mice; Microscopy; mouse corneal injury; reversion; Tomography, Optical Coherence; reversion; corneal stromal scar; keratocytes; cell therapy; mouse corneal injury
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25137053

Cell-based therapies using corneal stromal stem cells (CSSC), corneal keratocytes, or a combination of both suppress corneal scarring. The number of quiescent keratocytes in the cornea is small; it is difficult to expand them in vitro in quantities suitable for transplantation. This study examined the therapeutic effect of corneal fibroblasts reversed into keratocytes (rCF) in a mouse model of mechanical corneal injury. The therapeutic effect of rCF was studied in vivo (slit lamp, optical coherence tomography) and ex vivo (transmission electron microscopy and immunofluorescence staining). Injection of rCF into the injured cornea was accompanied by recovery of corneal thickness, improvement of corneal transparency, reduction of type III collagen in the stroma, absence of myofibroblasts, and the improvement in the structural organization of collagen fibers. TEM results showed that 2 months after intrastromal injection of cells, there was a decrease in the fibril density and an increase in the fibril diameter and the average distance between collagen fibrils. The fibrils were well ordered and maintained the short-range order and the number of nearest-neighbor fibrils, although the averaged distance between them increased. Our results demonstrated that the cell therapy of rCF from ReLEx SMILe lenticules promotes the recovery of transparent corneal stroma after injury.