Limbal stem cell transplantation: current perspectives

Abstract

Regeneration of the corneal surface after an epithelial insult involves division, migration, and maturation of a specialized group of stem cells located in the limbus. Several insults, both intrinsic and extrinsic, can precipitate destruction of the delicate microenvironment of these cells, resulting in limbal stem cell deficiency (LSCD). In such cases, reepithelialization fails and conjunctival epithelium extends across the limbus, leading to vascularization, persistent epithelial defects, and chronic inflammation. In partial LSCD, conjunctival epitheliectomy, coupled with amniotic membrane transplantation, could be sufficient to restore a healthy surface. In more severe cases and in total LSCD, stem cell transplantation is currently the best curative option. Before any attempts are considered to perform a limbal stem cell transplantation procedure, the ocular surface must be optimized by controlling causative factors and comorbid conditions. These factors include adequate eyelid function or exposure, control of the ocular surface inflammatory status, and a well-lubricated ocular surface. In cases of unilateral LSCD, stem cells can be obtained from the contralateral eye. Newer techniques aim at expanding cells in vitro or in vivo in order to decrease the need for large limbal resection that may jeopardize the “healthy” eye. Patients with bilateral disease can be treated using allogeneic tissue in combination with systemic immunosuppressive therapy. Another emerging option for this subset of patients is the use of noncorneal cells such as mucosal grafts. Finally, the use of keratoprosthesis is reserved for patients who are not candidates for any of the aforementioned options, wherein the choice of the type of keratoprosthesis depends on the severity of the disease. In summary, limbal stem cell transplantation improves both vision and quality-of-life in patients with ocular surface disorders associated with LSCD, and overall, the use of autologous tissue offers the best results. Future studies aim at improving cellular expansion and finding different sources of stem cells.

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

“…First of all, it is not clear if the small biopsies must be integrated and remain on the corneal surface forever, thus providing a stable source of corneal epithelium, a sort of “ectopic limbus,” or whether they should provide stem cells that will migrate onto the recipient cornea and repopulate the limbus. We should bear in mind that the migration process promotes stem cell differentiation and it has not yet been proven whether TA cells can redifferentiate into a stem cell state ([ 67 ]; Di [ 68 ]). Moreover, the amniotic membrane (AM), on which biopsies are glued, can both prevent and promote the correct engraftment and survival of the stem cells.…”

Results of simple limbal epithelial transplantation in unilateral ocular surface burn

“…On the other hand, even though literature review of CLAU shows that the ocular surface was improved in 82%–94% of the patients, the success was limited to patients in whom large grafts (>120°) were used. [ 15 16 ] In addition, visual acuity Dropped to 60% when smaller grafts were used. The exact amount of tissue from the healthy eye that can be transplanted safely without jeopardizing the donor eye is still debatable.…”

Clinical Outcomes From Cultivated Allogenic Stem Cells vs. Oral Mucosa Epithelial Transplants in Total Bilateral Stem Cells Deficiency

“…In addition to stem cells, niches consist also of non-stem cells, such as limbal stromal fibroblasts, melanocytes and immune cells which have the role of maintaining the stem cells dormant (1,2). Following an injury of the corneal surface, the limbal epithelial stem cells (LESCs) proliferate, divide, migrate and mature in order to ensure regeneration (3). LESCs are activated into transient amplifying cells, divide and migrate toward the center of the cornea in order to restore the surface.…”