Induced pluripotent stem cells as tool for cornea study in regenerative medicine

Abstract

Induced Pluripotent Stem Cells technology as tool for cornea study in regenerative medicine.The ocular surface consists of an epithelial surface with specialized regions, including cornea lacrimal gland and conjunctiva. Altogether, these regions play a role in vision maintenance by transmitting light and, as first eye layer, ensure protection for the whole eye.These major roles are subject to defective developments or imbalanced maintenance, due to genetic variants or cellular degeneration, respectively, causing vision‐related problems. Intensive research is performed world‐wide to develop new therapies for such vision defects by using in vitro models, but lack of eye donations or low viability is an obstacle for such assays. At the same time, variability among donors on their genetic or epigenetic background is the main barrier for reproducibility, in addition to advanced age of donor, which is a factor limiting cell expansion or present a high number of senescent cells.A promising approach is to use stem cells to generate ocular surface cells or tissue, by mimicking the embryo development. It exists multiple sources of stem cells able to in vitro models, adult corneal cells isolated from biopsies have the advantage to resemble the organ source, but the collection has the disadvantage to be invasive. An alternative and highly valuable approach to generate organoid is from pluripotent stem cells, carrying the potential to differentiate into most cell types of the body and are subdivided into embryonic stem cells, derived from the inner cell mass of preimplantation embryos, and induced pluripotent stem cells (IPSCs) reprogrammed from adult cells.As IPSCs are one of the most promising approaches to counteract this lack of donations, several assays were performed to select the best conditions to generate cornea cells. The main goal is to characterize the developmental procedure by growth factors modulation and assess the maturation degree for the final product. The most important aspect to generate such final product is the heterogeneity of cell population during differentiation or maturation, as epithelial cornea layer has a different cell origin in comparison to stroma or endothelial cornea.Once differentiation and maturation are achieved, this in vitro model can be used for multiple downstream applications. As therapeutic approaches, organoids can be used as a living biobank or to model corneal diseases, either by using cells from affected patients or by base editing, introducing a causative mutation into the genome. Either patient‐derived or control organoids have the high potential to develop gene therapy, optogenetics, be a source of transplantable cells to replace generating tissue or screen small molecules treatments.For this topic, we will focus on the IPSC technology to derive cornea tissue and its perspective for eye development studies, clinical or preclinical study by comparing the methodology depending of the potential applications.