Cultivated corneal epithelial stem cell transplantation in ocular surface disorders

Koizumi, Noriko; Inatomi, Tsutomu; Suzuki, Tomo; Sotozono, Chie; Kinoshita, Shigeru

doi:10.1016/s0161-6420(01)00694-7

Cited by 425 publications

(254 citation statements)

References 15 publications

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“…The results were similar to those reported in keratolimbal allograft transplantation (KLAL). 15,27,28 The rate of success seemed to be worse than the previous reports 1, 3,5,12 , and the difference was probably attributed to the differences in patient selection and preoperative condition.…”

Section: Discussionmentioning

confidence: 78%

“…[1][2][3][4][5][6][7][8][9][10][11][12][17][18][19][20][21][22][23][24][25][26] Although short-term outcomes appeared promising, only a few mid-term or long-term results have been reported. Validity of CLET for acute phase of chemical burns and SJS was reported, 6 however, the efficacy of the method for chronic cicatricial keratoconjunctivitis seems to be less dramatic.…”

Section: Discussionmentioning

confidence: 99%

“…31 They concluded that the denuded AM is the best carrier for corneal epithelial sheet preparation. 32 Also, Schwab believed that the remained amniotic epithelium would interfere with the potential adherence of expanded corneal epithelial cells to the AM. 33 Co-culture of feeder cells with epithelial cells have been shown to be beneficial for epithelial cell proliferation and stratification.…”

Section: Discussionmentioning

confidence: 99%

“…The method was first reported by Pellegrini et al in 1997, followed by several other investigators including our group. [1][2][3][4][5][6][7][8][9][10][11][12] In our previous report in 2002, the short-term outcomes of CLET were comparable with conventional limbal epithelial transplantation. 7 We found that the method did not produce excellent outcomes in patients with severe cicatricial ocular surface disorders such as Stevens-Johnson syndrome (SJS) and chemical/thermal burns of the cornea.…”

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confidence: 99%

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Factors Influencing Outcomes in Cultivated Limbal Epithelial Transplantation for Chronic Cicatricial Ocular Surface Disorders

Shimazaki

Higa

Morito

et al. 2007

American Journal of Ophthalmology

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Cultivated limbal epithelial transplantation (CLET) is a recently developedsurgical method to reconstruct the ocular surface in eyes with limbal dysfunction. The concept of the CLET is to produce a limbal epithelial sheet containing progenitor cells of the corneal epithelium, and then to transplant to the ocular surface following excision of cicatricial tissues. The method was first reported by Pellegrini et al in 1997, followed by several other investigators including our group. [1][2][3][4][5][6][7][8][9][10][11][12] In our previous report in 2002, the short-term outcomes of CLET were comparable with conventional limbal epithelial transplantation. 7 We found that the method did not produce excellent outcomes in patients with severe cicatricial ocular surface disorders such as Stevens-Johnson syndrome (SJS) and chemical/thermal burns of the cornea. 7 This may be due to the fact that many of the patients had risk factors for poor epithelialization such as decreased tear production, lid abnormalities, persistent inflammation. [13][14][15] It is not clear whether the relatively poor outcomes of our previous report can be improved by the modification of the epithelial sheet preparation. There are a variety of factors that may influence the quality of the epithelial sheet, which include; source of cells, preparation of the cells, types of substrates used, cultivation medium, the use of feeder cells, and culture conditions. Our group has made some modification of the cultivation/preparation methods including the use of feeder cells, cell suspension technique and air-lifting of the cell sheet.In order to investigate whether the modification resulted in improvement in surgical outcomes, we retrospectively studied the mid-term outcomes of CLET. The mid-term outcomes of CLET for chronic cicatricial ocular surface disorders were compared with the different cultivation methods. Also, other factors were analyzed to see if they influenced the results. METHODS PatientsTwenty nine eyes of 27 patients that had CLET between June 1999 and November 2003 were retrospectively analyzed in this study. Patients consisted of 16 males and 11 females, with a mean age of 50.2 + 20.7 years (15-82 years). All eyes had total limbal dysfunction. Conjunctivalization was confirmed preoperatively by impression cytology in 10 of 27 eyes. Mean corrected visual acuity was counting fingers, and two-third of the eyes had less than 20/2000. Schirmer`s test was performed in 21 eyes and decreased tear secretion (Schirmer`s value < 5 mm) was noted in 12 eyes. As for preoperative complications, glaucoma, macular degeneration, and lid deformity were noted in 4, 1, and 3 eyes, respectively.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Factors Influencing Outcomes in Cultivated Limbal Epithelial Transplantation for Chronic Cicatricial Ocular Surface Disorders

Shimazaki

Higa

Morito

et al. 2007

American Journal of Ophthalmology

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“…chemical burn. 20 By performing CCET, the cornea soon became re-epithelialized, and the vision was dramatically improved. However, as the cells were from irrelevant cadaveric donors, the recipients had to be immunosuppressed.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of cultivated oral mucosal epithelial cells for severe corneal burn

Kuo

et al. 2009

Eye

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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.

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Human Limbal Progenitor Cells Expanded on Intact Amniotic Membrane Ex Vivo

Grueterich

Tseng²

2002

Arch Ophthalmol

102

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Background: The transplantation of human limbal epithelium on amniotic membrane as a substrate is a new treatment for limbal stem cell deficiency. Limbal epithelial stem cells are characterized by a slow cell cycle and the lack of K3 keratin and connexin 43 (Cx43), a gap junction protein. We investigated Cx43 expression, gap junction intercellular communication (GJIC), and proliferative activity of limbal epithelium expanded on amniotic membrane. Methods: Connexin 43 expression and bromodeoxyuridine (BrdU) incorporation were determined by immunohistology. The GJIC was investigated by a scrapeloading dye transfer assay. Expression of Cx43 and K3 keratin as well as BrdU-retaining nuclei were also analyzed after xenotransplantation in nude mice. Results: Limbal epithelium showed mean±SD 12.4% ±14.5% positive units of Cx43 expression and a low BrdU labeling index of 2.4% ± 0.9% (n = 5), of which the latter was due to slow cycling, as proved by its increase to 62.0%±9.5% after continuous BrdU labeling for 5 days. Most of the expanded epithelium did not show GJIC (83%), significantly more than that grown on plastic (6%; PϽ.002). Basal cells of the stratified epithelium after xenotransplantation did not express Cx43 and K3 keratin, but their nuclei retained BrdU. Conclusion: These results support the hypothesis that intact amniotic membrane preferentially preserves and expands Cx43-negative, keratin K3-negative, and GJICdeficient limbal epithelium, a phenotype resembling that of stem cell-containing limbal basal epithelial cells in vivo. Clinical Relevance: Intact amniotic membrane is a suitable substrate for bioengineering limbal epithelia for ocular surface reconstruction.

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Cultivated corneal epithelial stem cell transplantation in ocular surface disorders

Cited by 425 publications

References 15 publications

Factors Influencing Outcomes in Cultivated Limbal Epithelial Transplantation for Chronic Cicatricial Ocular Surface Disorders

Factors Influencing Outcomes in Cultivated Limbal Epithelial Transplantation for Chronic Cicatricial Ocular Surface Disorders

Transplantation of cultivated oral mucosal epithelial cells for severe corneal burn

Human Limbal Progenitor Cells Expanded on Intact Amniotic Membrane Ex Vivo

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