Transplantation of cultivated oral mucosal epithelial cells for severe corneal burn

Abstract

Purpose To access the feasibility of using cultivated oral mucosal epithelial cell transplantation (COMET) for the management of severe corneal burn. Methods COMET was performed to promote re-epithelialization in two eyes with acute alkaline burn and one eye with chronic alkaline burn, and to reconstruct the ocular surface in two eyes with chronic thermal burn. Autologous oral mucosal epithelial cells obtained from biopsy were cultivated on amniotic membrane. Immunoconfocal microscopy for keratins and progenitor cell markers was performed to characterize the cultivated epithelial sheet. Following transplantation, the clinical outcome and possible complications were documented. The patients were followed for an averaged 29.6 ± 3.6 (range: 26-34) months. Results Cultivated oral mucosal epithelial sheet expressed keratin 3, 13, and progenitor cell markers p63, p75, and ABCG2. After COMET, all the corneas became less inflamed, and the corneal surface was completely reepithelialized in 6.0 ± 3.2 (range: 3-10) days in all but one patients. Microperforation occurred in one patient, and a small persistent epithelial defect developed in another. Both were solved uneventfully. In all patients, superficial corneal blood vessels invariably developed, and to further improve vision, conjunctivo-limbal autografting (N ¼ 3) and/or penetrating keratoplasty (N ¼ 3) were performed subsequently. The vision of all patients showed substantial improvement after additional surgeries. Conclusions This study showed the potential of COMET to promote re-epithelialization and reduce inflammation in acute corneal burn, and to reconstruct the corneal surface in chronic burn. COMET may, therefore, be considered an alternative treatment for severe corneal burn.

Expression of Angiogenesis-Related Factors in Human Corneas after Cultivated Oral Mucosal Epithelial Transplantation

“…COMET also can be used as an alternative treatment to promote reepithelialization and reduce inflammation in acute corneal chemical or thermal injuries. 13 Furthermore, long-term existence of transplanted oral mucosal stem/progenitor cells on the ocular surface also supports the rationale for clinical use of cultivated epithelial transplantation. 3 However, even after successful autologous COMET, various degrees of superficial corneal neovascularization (NV) can be detected beneath the transplanted epithelial sheet.…”

“…3 However, even after successful autologous COMET, various degrees of superficial corneal neovascularization (NV) can be detected beneath the transplanted epithelial sheet. [13][14][15][16] Clinically, corneal NV following total LSCD is the most severe type, and the molecular mechanisms regulating NV formation and restoration of corneal avascularity after CLET have been reviewed extensively. 17,18 Recently, in vitro studies using cultivated oral and corneal epithelial cells from either humans [19][20] or rabbits 20,21 have shown that decreased expression of thrombospondin-1 (TSP-1) 20 and soluble fms-like tyrosine kinase-1 (sFlt-1), 22 and increased secretion of fibroblast growth factor-2 (FGF-2) 21 may be responsible for the enhanced angiogenic potential after COMET.…”

Adult human buccal epithelial stem cells: identification, ex-vivo expansion, and transplantation for corneal surface reconstruction

“…24 Investigations on this variable have not been possible to date as there is no single, specific molecular marker for epithelial SCs, especially, as the known markers are not exclusive. 7,9,11,25 The reported putative markers for BMESCs include the transcription factor p63, 7 ATP-binding cassette transporter (ABCG2), 9,11 lowaffinity NGF receptor p75, 25 and b1 integrin. As these markers are not exclusive to SCs, it is essential to develop a specific method to identify and quantify the BMESCs.…”

“…[7][8][9] But the SC content in cultured buccal mucosal epithelium has not been analyzed, except for the reports on the expression of the putative SC markers like p63, ABCG2, p75, and b1 integrin that are not exclusive to SCs. 10,11 Other markersFa6 integrin and melanomaassociated chondroitin sulfate proteoglycan (MCSP)Fwere found to be restricted to clusters of cells in the mucosal papillay tips. 12 Previously, we have demonstrated that the two parametersFhigh expression of nuclear protein p63 and a greater nucleus/cytoplasmic (N/C) ratio in combinationFidentified a subset of limbal epithelial cells with SC phenotype.…”

Concise Review: Limbal Epithelial Stem Cell Therapy: Controversies and Challenges

“…COMET has been shown to be successful in restoring the corneal surface with follow-up times of up to 35 months [36][37][38][39][40][41][42][43]. A summary of the reported studies in human patients to date is shown in Table 1.…”