Repairing the corneal epithelium using limbal stem cells or alternative cell-based therapies

Abstract

The corneal epithelium is maintained by limbal stem cells (LSCs) that reside in the basal epithelial layer of the tissue surrounding the cornea termed the limbus. Loss of LSCs results in limbal stem cell deficiency (LSCD) that can cause severe visual impairment. Patients with partial LSCD may respond to conservative therapies designed to rehabilitate the remaining LSCs. However, if these conservative approaches fail or, if complete loss of LSCs occurs, transplantation of LSCs or their alternatives is the only option. While a number of clinical studies utilizing diverse surgical and cell culture techniques have shown favorable results, a universal cure for LSCD is still not available. Knowledge of the potential risks and benefits of current approaches, and development of new technologies, is essential for further improvement of LSCD therapies. Areas covered: This review focuses on cell-based LSCD treatment approaches ranging from current available clinical therapies to preclinical studies of novel promising applications. Expert opinion: Improved understanding of LSC identity and development of LSC expansion methods will influence the evolution of successful LSCD therapies. Ultimately, future controlled clinical studies enabling direct comparison of the diverse employed approaches will help to identify the most effective treatment strategies.

Process Development and Safety Evaluation of ABCB5+ Limbal Stem Cells as Advanced-therapy Medicinal Product to Treat Limbal Stem Cell Deficiency

“…Furthermore, current approaches are often associated with regulatory and logistical obstacles, seeing that the grafts contain variable numbers of LSCs and that the preparations have not been shown to be (cryo) preservable [43]. We hypothesized that surface marker-based prospective isolation, expansion and puri cation of LSCs from deceased donors might overcome these obstacles by precluding the transfer of potentially highly immunogenic cell subpopulations, ensuring de ned composition and purity of the cell product, and enabling storage and transportation [4,43]. In the light of this situation, we strived to develop and validate a GMP-compliant manufacturing process, by which ABCB5 + LSCs from cadaveric human limbal tissue can be expanded in vitro, isolated as a homogenous cell population and manufactured as a clinical-grade ATMP (Fig.…”

“…Under such circumstances, conjunctival epithelial cells can invade and successively replace corneal epithelial cells. As a result, corneal neovascularization, chronic in ammation and stromal scarring can occur, which may contribute to discomfort, corneal opaci cation, vision loss and even blindness [1][2][3][4]. According to a bulletin of the WHO, corneal disease is a major cause of blindness worldwide, second only to cataract [5].…”

“…Therapeutic options for LSCD depend on the etiology, severity of symptoms, extent (partial vs. total) and laterality (uni-vs. bilateral) of the disease [3,4,6,7]. Treatment of mild and moderate cases aims at the control of symptoms.…”

“…In these cases, recovery requires the presence of at least certain numbers of remaining LSCs that can restore the corneal epithelium. In severe LSCD, where no or insu cient amounts of LSCs are present, the LSC pool needs to be restored [4,7]. Earlier procedures involved transplantation of limbal tissue, either from the patient's healthy or less affected contralateral eye or, in cases of bilateral LSCD, from a living or deceased donor [8][9][10].…”

Corneal Stem Cells as a Source of Regenerative Cell-Based Therapy

“…A certain number of studies have been done to isolate and characterize multipotent stem cells from different tissues in order to use their great potential in regenerative medicine. Bone marrow-derived mesenchymal stem cells [83], human umbilical cord mesenchymal stem cells [84], postnatal periodontal ligament [85], and limbal stem cells [86] are recently studied stem cells sources in corneal wound healing and regeneration. Saghizadeh et al [30] have recently reviewed all major stem cell usage in corneal wound healing.…”