Limbal Stem-Cell Therapy and Long-Term Corneal Regeneration
Limbal Stem-Cell Therapy and Long-Term Corneal Regeneration
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DOI：
10.1056/nejmoa0905955
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发表时间：
2010-07-08
影响因子：
158.5
通讯作者：
Pellegrini, Graziella
中科院分区：
文献类型：
--
作者：
Rama, Paolo;Matuska, Stanislav;Pellegrini, Graziella
背景角膜的更新和修复是由角膜缘干细胞介导的，角膜缘干细胞位于角膜和球结膜之间的狭窄区域。眼部烧伤可能会破坏角膜缘，导致角膜缘干细胞缺乏。我们研究了细胞治疗烧伤相关性角膜破坏合并角膜缘干细胞缺乏症患者的长期临床结果。方法：我们使用纤维蛋白培养的自体角膜缘干细胞治疗112例角膜损伤患者，其中大多数患者存在烧伤相关性角膜缘干细胞缺乏症。临床结果采用Kaplan-Meier、Kruskal-Wallis、单因素和多因素Logistic回归分析进行评估。我们还根据全克隆形成干细胞的百分比来评估临床结果。结果76.6%的眼获得了透明的、可再生的角膜上皮永久修复。失败发生在第一年内。随着时间的推移，恢复的眼睛保持稳定，经过长达10年的随访(平均2.91+/-1.99；中位数1.93)。在后期分析中，成功--即在供体基质上产生正常上皮--与培养中p63-明亮的全克隆形成干细胞的百分比有关。在78%的患者中，p63-亮细胞占克隆细胞总数的3%以上的培养与移植成功有关。相比之下，在培养中，这些细胞占细胞总数的3%或更少，只有11%的患者与成功移植有关。移植失败也与最初的眼损伤类型和术后并发症有关。结论角膜缘干细胞的培养是治疗烧伤所致的人角膜破坏的一种移植细胞来源。
BACKGROUNDCorneal renewal and repair are mediated by stem cells of the limbus, the narrow zone between the cornea and the bulbar conjunctiva. Ocular burns may destroy the limbus, causing limbal stem-cell deficiency. We investigated the long-term clinical results of cell therapy in patients with burn-related corneal destruction associated with limbal stem-cell deficiency, a highly disabling ocular disease.METHODSWe used autologous limbal stem cells cultivated on fibrin to treat 112 patients with corneal damage, most of whom had burn-dependent limbal stem-cell deficiency. Clinical results were assessed by means of Kaplan-Meier, Kruskal-Wallis, and univariate and multivariate logistic-regression analyses. We also assessed the clinical outcome according to the percentage of holoclone-forming stem cells, detected as cells that stain intensely (p63-bright cells) in the cultures.RESULTSPermanent restoration of a transparent, renewing corneal epithelium was attained in 76.6% of eyes. The failures occurred within the first year. Restored eyes remained stable over time, with up to 10 years of follow-up (mean, 2.91 +/- 1.99; median, 1.93). In post hoc analyses, success - that is, the generation of normal epithelium on donor stroma - was associated with the percentage of p63-bright holoclone-forming stem cells in culture. Cultures in which p63-bright cells constituted more than 3% of the total number of clonogenic cells were associated with successful transplantation in 78% of patients. In contrast, cultures in which such cells made up 3% or less of the total number of cells were associated with successful transplantation in only 11% of patients. Graft failure was also associated with the type of initial ocular damage and postoperative complications.CONCLUSIONSCultures of limbal stem cells represent a source of cells for transplantation in the treatment of destruction of the human cornea due to burns.