Successful Clinical Implementation of Corneal Epithelial Stem Cell Therapy for Treatment of Unilateral Limbal Stem Cell Deficiency
Successful Clinical Implementation of Corneal Epithelial Stem Cell Therapy for Treatment of Unilateral Limbal Stem Cell Deficiency
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DOI：
10.1002/stem.276
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发表时间：
2010-03-31
期刊：
影响因子：
5.2
通讯作者：
Figueiredo, Francisco
中科院分区：
文献类型：
--
作者：
Kolli, Sai;Ahmad, Sajjad;Figueiredo, Francisco
角膜上皮由称为角膜缘干细胞（LSC）的干细胞群维持，这是由于它们位于称为利姆布斯的角膜外缘的基底层中。角膜缘干细胞缺乏症（LSCD）的治疗已经通过移植从利姆布斯的小活检中获取的离体扩增的LSC来实现。这是一项相对较新的技术，因此，尚未制定具体的国家或国际指南。由于缺乏这种具体的指导，我们的小组试图通过对目前使用的研究方法进行某些修改来尽量减少对患者的任何风险。其中包括更换培养系统中的所有非人动物产品，以及在药品生产质量管理规范条件下生产所有试剂和培养物。此外，第一次，一个严格定义的统一组的患者与总单侧LSCD和没有其他显着的眼部条件已被用来允许成功或失败的治疗LSCD直接归因于拟议的干细胞治疗。使用一项具有严格入选和排除标准的前瞻性设计研究从我们的单侧LSCD患者数据库中招募患者。本研究纳入了8例单侧全LSCD患者的8只眼，这些患者接受了人羊膜（HAM）上的体外扩增自体LSC移植治疗，平均随访时间为19（RANGE）个月。术后，所有患眼（100%）获得了满意的眼表重建和稳定的角膜上皮。最后一次检查时，5只眼最佳矫正视力提高，3只眼保持不变。所有患者的视力损害和疼痛评分均有所改善（p <0.05）。这项研究表明，在不使用非人动物细胞或产品的情况下，移植在HAM上培养的自体角膜缘上皮干细胞是一种安全有效的方法，可以重建单侧全LSCD患者的角膜表面并恢复有用的视力。干细胞2010; 28：297-610
The corneal epithelium is maintained by a population of stem cells known as limbal stem cells (LSCs) due to their location in the basal layer of the outer border of the cornea known as the limbus. Treatment of limbal stem cell deficiency (LSCD) has been achieved with transplantation of ex vivo expanded LSCs taken from a small biopsy of limbus. This is a relatively new technique, and as such, specific national or international guidance has yet to be established. Because of the lack of such specific guidance, our group has sought to minimize any risk to the patient by adopting certain modifications to the research methodologies in use at present. These include the replacement of all non-human animal products from the culture system and the production of all reagents and cultures under Good Manufacturing Practice conditions. In addition, for the first time, a strictly defined uniform group of patients with total unilateral LSCD and no other significant ocular conditions has been used to allow the success or failure of treating LSCD to be attributable directly to the proposed stem cell therapy. A prospectively designed study with strict inclusion and exclusion criteria was used to enroll patients from our database of patients with unilateral LSCD. Eight eyes of eight consecutive patients with unilateral total LSCD treated with ex vivo expanded autologous LSC transplant on human amniotic membrane (HAM) with a mean follow-up of 19 (RANGE) months were included in the study. Postoperatively, satisfactory ocular surface reconstruction with a stable corneal epithelium was obtained in all eyes (100%). At last examination, best corrected visual acuity improved in five eyes and remained unchanged in three eyes. Vision impairment and pain scores improved in all patients (p < .05). This study demonstrates that transplantation of autologous limbal epithelial stem cells cultured on HAM without the use of non-human animal cells or products is a safe and effective method of reconstructing the corneal surface and restoring useful vision in patients with unilateral total LSCD. STEM CELLS 2010; 28: 297-610