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

Abstract

Total bilateral limbal stem cell deficiency results from various pathologies, from burns (either chemical or physical) to Sjogren Syndrome, aniridia or ocular cicatricial pemphigoid. After the loss of stem cells, normal corneal epithelium is replaced by a more opaque and vascularized conjunctival epithelium, causing loss of vision. After 1997, cultivation techniques for limbal stem cells became possible. In parallel, cultivation techniques for oral mucosa epithelial cells were also available. The aim of our review was to summarize the clinical outcomes following allogenic cultured limbal stem cell transplant (allogenic CLET), and on the other hand, oral mucosa derived epithelium transplant (cultivated oral mucosa epithelial transplant-COMET or cultivated autologous oral mucosal epithelial cell sheet-CAOMECS), in the case of total bilateral limbal stem cell loss. Thirty studies matching the inclusion criteria were found. The clinical improvement in both methods was reported similar, with percentages higher than 50% of the treated cases. However, the comparison between studies was difficult to achieve due to the lack of a universal and objective grading tool for assessing post-operative results. The definition of clinical improvement was problematic, because success was defined differently, depending on the study. Moreover, some of the studies followed both autologous and allogenic CLET, but described the results together, for both procedures, and therefore it was impossible to analyze them separately. COMET presented some advantages compared to CLET. By using autologous cells, there was no risk of immune activation and no immunosuppression was needed. COMET, however, might be associated with increased risk of persistent epithelial defects and graft failure, compared with allogenic CLET.

Stem Cells in the Path of Light, from Corneal to Retinal Reconstruction

“…However, immunological rejection and outcomes seemed to be similar in both techniques, as described by various authors (Satake et al [ 22 ] and Parihar et al [ 23 ]), while keratolimbal allograft did not require as many resources as the cultivation technique. Clinical outcomes of AlloCLET were reviewed in depth in 2020 [ 24 ].…”

Current Perspectives of Limbal-Derived Stem Cells and its Application in Ocular Surface Regeneration and Limbal Stem Cell Transplantation

“…Nevertheless, persistent epithelial defects and graft failure were higher in COMET compared to allo-CLET. 73 With the advent of CLET and SLET, several other cell sources are also being explored in treating LSCD. Specifically, induced pluripotent stem cells (iPSCs) offer a promising approach to generate mature corneal/limbal epithelium with 3D corneal organoids.…”

“…Nevertheless, persistent epithelial defects and graft failure were higher in COMET compared to allo‐CLET. 73 …”

Differentiation Induction of Human Stem Cells for Corneal Epithelial Regeneration

“…After the differentiation induction for 21 days, the result revealed incomplete differentiation because they expressed CK3 but did not express CK12. Oral mucosa epithelium is the source of adult cells which are widely used for corneal epithelium reconstruction [ 6 , 139 , 140 , 141 , 142 ]. The oral mucosa epithelial cells cultured on amniotic membranes offered satisfied outcomes after transplantation in patients in clinical trials.…”

“…Even though this procedure is effective and has high success rate of 70–80% [ 4 ], it is unable to be applied to patients with bilateral LSCD. Transplantation of allogeneic limbal epithelial cells is an optional strategy but it has a risk of graft rejection [ 6 , 7 , 8 ]. To avoid the lack of autologous limbal epithelium and high risk of graft failure from allogeneic sources, autologous stem cells become a promising option for the regeneration of corneal epithelial tissue.…”