North East Institute for Stem Cell Research, International Centre for Life, NE1 3BZ, United Kingdom.
Stem Cells. 2010 Mar 31;28(3):597-610. doi: 10.1002/stem.276.
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.
角膜上皮由被称为角膜缘干细胞（limbal stem cells，LSCs）的干细胞群体维持，这是由于它们位于角膜外边界的基底层，即角膜缘。通过从小部分角膜缘活检中获取体外扩增的 LSCs 并进行移植，已经实现了对角膜缘干细胞缺乏症（limbal stem cell deficiency，LSCD）的治疗。这是一种相对较新的技术，因此，尚未制定特定的国家或国际指南。由于缺乏此类特定的指导，我们的团队通过对目前使用的研究方法进行某些修改，旨在将对患者的任何风险降至最低。这些修改包括从培养系统中替换所有非人类动物产品，并在良好生产规范条件下生产所有试剂和培养物。此外，我们首次使用严格定义的、统一的单侧完全 LSCD 且无其他显著眼部疾病的患者组，以使 LSCD 的治疗成功或失败能够直接归因于拟议的干细胞治疗。这项前瞻性设计的研究采用严格的纳入和排除标准，从我们单侧 LSCD 患者数据库中招募患者。纳入了 8 例单侧完全 LSCD 患者的 8 只眼，对其进行了体外扩增的自体 LSC 移植，移植在人羊膜（human amniotic membrane，HAM）上，平均随访时间为 19（范围）个月。所有眼（100%）术后均获得满意的眼表重建和稳定的角膜上皮。末次随访时，5 只眼最佳矫正视力提高，3 只眼无变化。所有患者的视力损害和疼痛评分均有所改善（p <.05）。这项研究表明，在不使用非人类动物细胞或产品的情况下，将 HAM 上培养的自体角膜缘上皮干细胞进行移植是一种安全有效的方法，可用于重建单侧完全 LSCD 患者的角膜表面并恢复有用视力。
