Corneal reconstruction with tissue-engineered cell sheets composed of autologous oral mucosal epithelium
Corneal reconstruction with tissue-engineered cell sheets composed of autologous oral mucosal epithelium
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DOI：
10.1056/nejmoa040455
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发表时间：
2004-09-16
影响因子：
158.5
通讯作者：
Tano, Y
中科院分区：
文献类型：
--
作者：
Nishida, K;Yamato, M;Tano, Y
背景：眼外伤或疾病可导致严重的角膜混浊，从而导致角膜上皮干细胞完全丧失所致的严重视力丧失。自体角膜干细胞来源的移植是同种异体移植的替代方案，不需要免疫抑制，但在许多双眼疾病导致双眼完全角膜干细胞缺陷的情况下，这是不可能的。我们研究了利用自体口腔粘膜上皮细胞作为重建角膜表面的细胞来源。方法：我们采集了4例双侧全角膜干细胞缺陷症患者的口腔粘膜组织标本。将收获的细胞在温度敏感的细胞培养表面上培养2周，然后用丝裂霉素C处理的3T3饲养层细胞在体外构建组织工程化上皮细胞片。在手术切除结膜纤维血管组织后，将经简单降温处理的培养的自体细胞片直接移植到裸露的角膜表面(每例患者1只眼)，不缝线。结果：4只处理眼在1周内角膜表面完全上皮化。术后4只眼均恢复角膜透明，视力明显提高。在平均14个月的随访期内，所有角膜表面保持透明。结论：自体口腔黏膜上皮细胞构成的无载体细胞片可用于重建角膜表面，并能恢复双侧严重眼表疾病患者的视力。
Background: Ocular trauma or disease may lead to severe corneal opacification and, consequently, severe loss of vision as a result of complete loss of corneal epithelial stem cells. Transplantation of autologous corneal stem-cell sources is an alternative to allograft transplantation and does not require immunosuppression, but it is not possible in many cases in which bilateral disease produces total corneal stem-cell deficiency in both eyes. We studied the use of autologous oral mucosal epithelial cells as a source of cells for the reconstruction of the corneal surface.Methods: We harvested 3-by-3-mm specimens of oral mucosal tissue from four patients with bilateral total corneal stem-cell deficiencies. Tissue-engineered epithelial-cell sheets were fabricated ex vivo by culturing harvested cells for two weeks on temperature-responsive cell-culture surfaces with 3T3 feeder cells that had been treated with mitomycin C. After conjunctival fibrovascular tissue had been surgically removed from the ocular surface, sheets of cultured autologous cells that had been harvested with a simple reduced-temperature treatment were transplanted directly to the denuded corneal surfaces (one eye of each patient) without sutures.Results: Complete reepithelialization of the corneal surfaces occurred within one week in all four treated eyes. Corneal transparency was restored and postoperative visual acuity improved remarkably in all four eyes. During a mean follow-up period of 14 months, all corneal surfaces remained transparent. There were no complications.Conclusions: Sutureless transplantation of carrier-free cell sheets composed of autologous oral mucosal epithelial cells may be used to reconstruct corneal surfaces and can restore vision in patients with bilateral severe disorders of the ocular surface.