Repair of corneal damage with stem cells

Abstract

The essence of regeneration and plasticity lies in the capacities of certain cell populations to give rise to progenies with specific functional and morphological traits. An array of molecular events directs this process (for instance, activation and de-activation of transcription or regulation of epigenetic mechanisms and controls). The unravelling of the processes that activate differentiation or de-differentiation events and the isolation and precise characterization of specific stem cell populations will open new avenues of therapy intervention in all areas of regenerative medicine, including eye pathologies. In the human anterior segment of the eye, adult stem cells can be found in the corneal limbus (the rim that separates cornea and conjunctiva). Currently, different approaches use transplantation of limbal epithelial stem cells (LESC) or corneal stromal stem cells (CSSC) to restore damaged cornea. LESC and CSSC establish a molecular dialogue that may support the maintenance of their stem phenotype. To restore corneal transparency and function other therapy approaches include the use of adult stem cells of different origins, bioengineered cells and biomaterials. Introduction According to The World Health Organization (WHO), corneal blindness (5.1% of total cases of blindness or visual deterioration) represents the fourth cause of blindness globally, after cataract, glaucoma and age-related macular degeneration (AMD). Updated advances in the application of stem cells to treat diseased cornea are reviewed in this work. Also, plasticity, “stemness” and regeneration are considered in the field of therapy endeavours targeted to tackle corneal pathologies. Stem cells have an essential role in development, tissue replacement and tissue repair. They reside in niches where an orchestrated ensemble of autocrine, paracrine and endocrine factors regulate their function and fate [1-3]. Stem cells are able to proliferate and differentiate into different cell types. Hence they are very important in cell renewal, both naturally and as a therapy tool. Difficulties in effective treatments are sometimes due to the significant extent and gravity of the lesion produced by both external insults (such as pathogenic agents or accidental damage due to burn or chemical corrosion) and genetic abnormality or ill-function. The search for new and effective treatments to restore vision is therefore a paramount. It is in this context where cell therapy may have an important niche of action. To regenerate a tissue to its partial or complete functional state new cells with high transformation potential should be obtained. Therefore, regeneration is based on appropriate replacement. Cell can be reprogrammed to an undifferentiated state from a differentiated one [4,5]. Also, some cell populations may shift among different states of differentiation. Anuran amphibians, for example, are able to regenerate the retina by means of a transdifferentiation process of the retinal pigmented epithelium and obtain a new lens from dorsal iris pigmented epithelium [6]. Cell differentiation is an intricate route that may progress in different directions. The complexities recline in molecular “orders” that carve the final fully functional cell. But the process can, at certain points, be stopped or reversed in opposite direction, thus making the pathway more flexible and prone to required adaptations [4,7]. In general, the term “stemness” refers to the dormant state and the capacity that some cells have to differentiate in given conditions [8]. But the expression incorporates different transformation capacities (totipotent stem cells exhibit the potential to generate any cell of an organism; an embryonic stem cell, however, generates all the cells of a given organism, but the trophoblast, and the production of progenies by postnatal stem cells is restricted to the tissue where they dwell [8,9]. Common characteristics of stem cells are their ability to divide and maintain their division potential or differentiate and loose such capacity [10]. Cell division can be symmetrical, where two identical cells are generated. When cell division is asymmetrical, one daughter cell keeps “stemness” whereas the other differentiates [8,10]. How and when the cell “decides” between symmetrical and asymmetrical divisions is not fully known but both external and intrinsic factors are involved [10]. The molecular machinery (noteworthy, control and modulation of transcription) responsible for the capacity of a cell to maintain a given state of “stemness” reacts to different and numerous stimuli [11,12]. It is important therefore to define the molecular events that determine cell potencies and fates. Once we have the knowledge, and expertise, Correspondence to: F. David Rodriguez, Department of Biochemistry and Molecular Biology, Group BMD, Faculty of Chemical Sciences, University of Salamanca, E-37007 Salamanca, Spain, Tel: +34 923294698, Fax: +34 923294579, E-mail: lario@usal.es