Peculiarities of reparative corneal regeneration applying stem cell secretome

Abstract

Introduction. Regenerative medicine is a promising and actively developing scientific area. Of particular interest are studies related to the mechanisms of biological drug action, a particular focus being on secretomes. The term “secretomes” refers to numerous cytokines, growth factors, and other proteins and peptides that are secreted by cells and regulate biological processes. Most published literature on biologi-cal effects of individual cytokines and cell secretomes during reparative regeneration processes have been carried out in vitro. Studies describing morphological control, i.e. assessing structural changes in tissue and identifying the key processes influenced by cytokines during regeneration, are scarce, and further research is needed. This article presents the results of evaluating the reparative corneal regeneration with secretome produced by mesenchymal stem cells (MSCs). Materials and methods. We divided guinea pigs (N=30) into three groups (experimental, comparison, and control). Under isoflurane anesthesia, each animal received a mechanical corneal defect 5 mm in diameter affecting 2/3 of the cornea in depth. We observed the animals and performed daily ophthalmological examinations. Animals were sacrificed on days 1, 5, 11, and 28 after the manipulation with an overdose of anesthesia. Then, we performed histological and micromorphometric evaluation. Results. We revealed that under the influence of cytokines, corneal regeneration was with less pronounced inflammation and exudation. The restoration of corneal curvature was full whereas that of corneal transparency was partial. Microscopic examination of the samples obtained from the animals of the experimental group showed that they had a lower inflammatory cell response, earlier epithelialization, restored thickness of the regenerate, and less scar-like tissue formation in the cornea than those in the comparison and control groups. We observed the appearance of hypovascular and avascular foci in the structure of the regenerate connective tissue, which may be associated with the remodeling process. This factor may also be responsible for the observed partial restoration of corneal transparency. Conclusion. The secret of stem cells has a positive effect on the healing of corneal wounds. The inflammation is moderate. The corneal regenerate is of nubecula type; corneal transparency is partially restored. Keywords: mesenchymal stem cells, secretome, cytokines, cornea, wound, reparative regeneration