Stem cell-based therapy for treating limbal stem cells deficiency: A review of different strategies

Abstract

The self renewal capability of limbal epithelial stem (LEST) cells is fundamental to the maintenance and healing of corneal epithelium. Limbal stem cell deficiency (LSCD), due to dysfunction or loss of LEST cells, therefore presents as persistent epithelial defects, corneal vascularization, conjunctivalization etc. Stem cell-based therapy, in its simplest form - limbal autograft, has been used successfully for more than a decade. For bilateral LSCD, similar approaches with limbal allografts have been unsuccessful largely due to strong immune rejection. Therefore, as an alternate strategy for treating bilateral LSCD, ex vivo expansion of the remaining LEST cells or autologous stem cells sourced from other potential sites is being explored. Different culture systems (with and without xenobiotic supplements) using substrates like amniotic membrane or fibrin gels have been used successfully for ex vivo LEST cell maintenance and reproduction by imitating the stem cell niche. This paper is organized into sections reviewing the LEST cells, LSCD and various stem cell-based approaches for treating LSCD and discussing future direction and challenges.

Treatment of Inherited Eye Defects by Systemic Hematopoietic Stem Cell Transplantation

“…2 Stem cell transplantation represents an attractive alternative for focal corneal repair, for example with limbal epithelial stem cells to repair corneal epithelium, 3 and with mesenchymal stem cells (MSCs) that have been shown to migrate and promote corneal healing, secrete soluble factors, and suppress inflammation and angiogenesis. 4 However, repairing hereditary eye deficiencies with stem cells has remained relatively unexplored.…”

A Review of Limbal Stem Cell Deficiency

“…49 There are many surgical approaches that have been developed over the past 2 decades in the management of LSCD. 13,[50][51][52] All limbal transplantations provide either allogeneic or autologous cell sources for the graft. Partial LSCD can use autologous limbal tissue from the uninvolved eye.…”

Bir Köpekte Limbal Kök Hücre Yetmezliğinin Tanısında Korneal İmpresyon Sitolojisi: Olgu Sunumu

“…Investigations in human LSCD patients yielded the identification of several factors in primary (congenital) etiology of the disease. Aniridia associated with PAX6 mutations [9] , ectrodactyl-ectodermal-dysplasia-clefting syndrome, keratitis-ichthyosis-deafness syndrome, xeroderma pigmentosum, dominant congenital keratitis and dyskeratosis congenita result in primary LSCD. On the other hand, inflammatory features of Steven-Johnsons Syndrome [10] , ocular cicatricial pemphigoid [11] , graft versus host disease, vernal keratoconjunctivitis [12] are implicated in the etiology of secondary LSCD.…”

“…Furthermore, chemical-thermal injuries, multiple surgical interventions including limbal region, chronic mechanical microtrauma induced by contact lens and inflammatory diseases of ocular surface are reported to cause LSCD [3,5,6,10,12] . Additionally, diabetes and vitamin A deficiency have a role in the development of LSCD [9] . LSCD develops in albino rats with induced type 2 diabetes mellitus as a result of diabetic keratopathy.…”