Cell therapy for corneal regeneration: Current status and future perspectives
Authors: Casaroli Ricardo 
Published: December 2022

Currently, the treatment of many serious ocular pathologies that affect the cornea focuses on the repair and regeneration of the affected structures—epithelium and endothelium—through cell therapy. On the ocular surface, there is a population of multipotent progenitor cells (limbal stem cells; LSC), located in the sclerocorneal limbus, which have a high proliferative, differentiating and regenerative capabilities. On the other hand, the corneal endothelium—the innermost corneal layer with little regenerative capacity in vivo—is responsible for controlling corneal homeostasis and transparency. Dysfunctions of both cell types—corneal epithelial and endothelial cells—are the leading cause of recoverable corneal blindness. Mesenchymal stem cells (MSCs) from adult tissue, obtained from adipose tissue and bone marrow aspirates, have the capacity for adipogenesis, osteogenesis, chondrogenesis, myogenesis and neurogenesis in vitro. However, its true potential towards epithelial differentiation seems to be limited, and its great clinical applicability seems to lie in its contribution to the homeostasis of the cellular microenvironment. Recent developments in the field of somatic cell reprogramming by induced pluripotent stem cells (IPSC) provide an exciting possibility for its future clinical application. Pluripotent stem cells can be obtained from different sources of adult tissue, among which IPSC (induced pluripotent stem cells) have excellent plasticity. Its ability to differentiate into corneal epithelial and endothelial phenotypes is still poorly understood. Likewise, in vitro organoid production methods are presented as an option for obtaining compromised and/or partially differentiated cell lines. In the meantime, their clinical use will require specific application and receptor safety so that they can correctly regenerate tissue, with added effort for adaptation of ‘clinical grade’ protocols. In this sense, the ocular tissue is characterized as an excellent candidate for a possible clinical application, since it constitutes a tissue with immune privilege, it is ‘isolated’ (intraocular spaces) from the other components of the body and also had a highly sophisticated avascular (cornea) and highly differentiated (retina and pigment epithelium) tissues. The possibility of establishing specific clinical‐grade protocols for cell differentiation and identifying specific cellular and molecular behaviour would contribute to a better understanding of the mechanisms involved in repair processes. One of the equally relevant aspects in advanced cell‐based therapies applied to corneal regeneration is related to the ideal composition of the extracellular matrix proteins and biocompatible/biomimetic substrates—artificial or natural—that may contribute to better cell differentiation and adaptation. All this would open innovative perspectives for a more rational and effective treatment of different pathologies associated with human corneal blindness, in the field of regenerative medicine through the application of advanced cell therapy.