Limbal Stem Cell Deficiency and Treatment with Stem Cell Transplantation

Abstract

The cornea is the outermost tissue of the eye and it must be transparent for the maintenance of good visual function. The superficial epithelium of the cornea, which is renewed continuously by corneal stem cells, plays a critical role in the permanence of this transparency. These stem cells are localized at the cornea-conjunctival transition zone, referred to as the limbus. When this zone is affected/destroyed, limbal stem cell deficiency ensues. Loss of limbal stem cell function allows colonization of the corneal surface by conjunctival epithelium. Over 6 million people worldwide are affected by corneal blindness, and limbal stem cell deficiency is one of the main causes. Fortunately, it is becoming possible to recover vision by autologous transplantation of limbal cells obtained from the contralateral eye in unilateral cases. Due to the potential risks to the donor eye, only a small amount of tissue can be obtained, in which only 1-2% of the limbal epithelial cells are actually limbal stem cells. Vigorous attempts are being made to expand limbal stem cells in culture to preserve or even enrich the stem cell population. Ex vivo expanded limbal stem cell treatment in limbal stem cell deficiency was first reported in 1997. In the 20 years since, various protocols have been developed for the cultivation of limbal epithelial cells. It is still not clear which method promotes effective stem cell viability and this remains a subject of ongoing research. The most preferred technique for limbal cell culture is the explant culture model. In this approach, a small donor eye limbal biopsy is placed as an explant onto a biocompatible substrate (preferably human amniotic membrane) for expansion. The outgrowth (cultivated limbal epithelial cells) is then surgically transferred to the recipient eye.Due to changing regulations concerning cell-based therapy, the implementation of cultivated limbal epithelial transplantation in accordance with Good Laboratory Practice using xenobiotic-free systems is becoming widely accepted both in Turkey and worldwide.

Defining compartmentalized stem cell populations with distinct cell division dynamics in the ocular surface epithelium

“…Studies to define and control corneal and conjunctival SCs would be of great clinical value for the treatment of extensive ocular injuries such as severe chemical burns or inflammatory diseases, e.g., Stevens-Johnson syndrome ( Barut Selver et al, 2017 ). Our genetic tools can be used to further investigate the cellular and molecular mechanisms of SC plasticity in different disease or injury models in vivo and to identify potential therapeutic strategy for limbal SC deficiency.…”

“…It is plausible that the limbal SCs may play an inhibitory role for conjunctival SCs to enter the corneal compartment during homeostasis, whereas elimination of limbal SCs by chemical injury might lead to conjunctivalization of the eye. Thus, our data reveals functional cross-interaction between SC types in the ocular epithelium and demonstrates their plasticity in response to tissue damage.Development • Accepted manuscriptStudies to define and control corneal and conjunctival SCs would be of great clinical value for the treatment of extensive ocular injuries such as severe chemical burns or inflammatory diseases, e.g., Stevens-Johnson syndrome(Barut Selver et al, 2017). Our genetic tools can be used to further investigate the cellular and molecular mechanisms of SC plasticity in different disease or injury models in vivo and to identify potential therapeutic strategy for limbal SC deficiency.…”

Time-course single-cell RNA sequencing reveals transcriptional dynamics and heterogeneity of limbal stem cells derived from human pluripotent stem cells

“…Other than self-renewal capability for homeostasis maintenance, LSCs have unipotency to differentiated into corneal epithelial cells and play vital roles in corneal regeneration and repair [ 4 ]. However, internal or external factors, such as genetic mutations, chemicals, burns, bacteria etc., could result in limbal malfunction, and limbal stem cells deficiency (LSCD), and lead to reduced vision and blindness [ 5 – 7 ].…”

Limbal Stem Cell Transplantation: Clinical Results, Limits, and Perspectives

“…Various protocols for the cultivation of limbal stem cells for transplantation have been proposed, including methods to extract cells from biopsy (mechanical disruption or enzymatic dissociation), different substrates and carriers (fibrin sheet, amniotic membrane, contact lenses, and collagen), and the presence of animal-derived or xeno-free components in the system (medium and feeder layer) [ 78 , 79 ]. Although good clinical outcomes have been reported with several different culture procedures, few studies have evaluated the clonal characteristics and proliferative potential of the cultivated cells.…”