TRANSPLANTATION OF EXPANDED LIMBAL EPITHELIAL STEM CELLS

描述(由申请人提供)：表现为角膜缘干细胞缺乏的角膜疾病仍然是临床医生最难处理和最具挑战性的情况之一。自1995年Pi重新引入保存的人羊膜移植用于眼表重建以来，许多研究表明羊膜移植在促进上皮创面愈合、减少基质炎症、减少瘢痕形成和减少不必要的新生血管形成方面是有效的。羊膜移植用于眼表重建已被FDA和Medicare批准。在RO1 EY06819的支持下，PI已经收集了足够的实验室和临床前的兔数据，以支持这样的假设，即这种保存的羊膜也是恢复成功地体外扩增角膜缘上皮干细胞所必需的“基质生态位”的理想基质。PI已获得美国食品和药物管理局(FDA)的IND(编号10313)和IRB的批准，通过进行I期临床试验将上述基础研究转化为临床应用，以实现以下两个目标： 目的1：证实自体体外扩增的角膜缘上皮干细胞移植的安全性和有效性。 单侧全角膜缘干细胞缺乏症的角膜表面重建。 目的2：证实同种异体体外扩增的角膜缘上皮干细胞移植的安全性和有效性。 双侧全角膜缘干细胞缺乏症的角膜表面重建。 这项临床试验的完成将首次证明，所述新的手术技术可以用来缓解症状，恢复完全角膜缘干细胞缺乏症患者的视力。在随后的临床试验中，随着进一步的修改和改进，这项新技术可能会开发成商业产品(FDA将其归类为生物制品)。此外，基于FDA的cGMP指南的体外操作平台，未来还可能通过针对扩张的角膜缘上皮干细胞的基因治疗来开发新的治疗方法。

DESCRIPTION (provided by applicant): Corneal diseases manifesting limbal stem cell deficiency remain to be one of the most difficult and challenging conditions for clinicians to manage. Ever since PI's reintroduction in 1995 of transplantation of preserved human amniotic membrane for ocular surface reconstruction, a number of studies have shown that amniotic membrane transplantation is effective in facilitating epithelial wound healing, and reducing stromal inflammation, scarring and unwanted new blood vessel formation. Amniotic membrane transplantation for ocular surface reconstruction has been approved by FDA and Medicare. Under RO1 EY06819 support, PI has gathered sufficient laboratory and pre-clinical rabbit data to support the hypothesis that such preserved amniotic membrane is also an ideal substrate to restore the "stromal niche" essential for successful ex vivo expansion of limbal epithelial stem cells. PI has obtained an IND (No.10313) from US Food & Drug Administration (FDA) and an IRB approval to translate the aforementioned basic research to clinical application by conducting a Phase I clinical trial to accomplish the following two Aims: Aim 1: To confirm the safety and efficacy of autologous ex vivo expanded limbal epithelial stem cells for reconstructing corneal surfaces with unilateral total limbal stem cell deficiency. Aim 2: To confirm the safety and efficacy of allogeneic ex vivo expanded limbal epithelial stem cells for reconstructing corneal surfaces with bilateral total limbal stem cell deficiency. Completion of this clinical trial will prove, for the first time that the said new surgical technique can be used to alleviate symptoms and to restore sights for patients inflicted with total limbal stem cell deficiency. With further modification and improvement made during subsequent clinical trials, this new technology may be developed into a commercial product (FDA's classification as a "Biologics"). Furthermore, from such a platform of ex vivo manipulation based on FDA's cGMP guidelines, new therapeutics may also be developed in the future by gene therapies targeted at expanded limbal epithelial stem cells.