Understanding cornea epithelial stem cells and stem cell deficiency: Lessons learned using vertebrate model systems

Abstract

Summary Animal models have contributed greatly to our understanding of human diseases. Here, we focus on cornea epithelial stem cell (CESC) deficiency (commonly called limbal stem cell deficiency, LSCD). Corneal development, homeostasis and wound healing are supported by specific stem cells, that include the CESCs. Damage to or loss of these cells results in blindness and other debilitating ocular conditions. Here we describe the contributions from several vertebrate models toward understanding CESCs and LSCD treatments. These include both mammalian models, as well as two aquatic models, Zebrafish and the amphibian, Xenopus. Pioneering developments have been made using stem cell transplants to restore normal vision in patients with LSCD, but questions still remain about the basic biology of CESCs, including their precise cell lineages and behavior in the cornea. We describe various cell lineage tracing studies to follow their patterns of division, and the fates of their progeny during development, homeostasis, and wound healing. In addition, we present some preliminary results using the Xenopus model system. Ultimately, a more thorough understanding of these cornea cells will advance our knowledge of stem cell biology and lead to better cornea disease therapeutics.

Generation of a Biomimetic Substitute of the Corneal Limbus Using Decellularized Scaffolds

“…In cases with unilateral disease, LSCD can be treated by transplanting autologous limbal tissue from a healthy eye to a damaged eye [5]. Autologous grafts are free from the risk of immune rejection, but are not available in bilateral cases and can potentially compromise the healthy donor eye, resulting in LSCD [6]. If an autologous transplant is not available, patients can be treated with allogeneic limbal grafts obtained from cadaveric Pharmaceutics 2021, 13 or living donors [5,6].…”

“…Autologous grafts are free from the risk of immune rejection, but are not available in bilateral cases and can potentially compromise the healthy donor eye, resulting in LSCD [6]. If an autologous transplant is not available, patients can be treated with allogeneic limbal grafts obtained from cadaveric Pharmaceutics 2021, 13 or living donors [5,6]. Allogeneic grafts are also subjected to important concerns, such as the risk of immune rejection [5] and graft survival [7].…”

“…The lack of a fully safe and efficient treatment makes necessary the search of therapeutic alternatives. In this regard, the development of cell culture methods allowing cell isolation and expansion is a major advance in the treatment of LSCD [6]. Using small limbal tissue biopsies, current technology allows the generation of limbal stem cell populations that can be implanted in patients with LSCD [8].…”

PCL Scaffold Combined with Rat Tail Collagen Type I to Reduce Keratocyte Differentiation and Prevent Corneal Stroma Fibrosis after Injury.

“…All authors have given approval to the nal version of the manuscript. 1 These authors contributed equally.…”

“…The cornea is a dome-shaped transparent tissue that functions as an optical lens that provides indispensable features to the visual system, including optical transparency and light refraction [1,2]. Meanwhile, the cornea is exposed to a constantly changing external environment as the outermost layer of the eye and is thus most likely to sustain damage; there are more than 1.52 million new cases of corneal blindness reported for each year [3], of which only less than 5% of patients have opportunities for corneal transplantation due to severe shortage of donor cornea and the high cost of transplantation surgery [4,5].…”