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管理的最困难和最具挑战性的疾病之一。自从PI在1995年重新引入移植保存的人羊膜用于眼表重建以来，许多研究表明羊膜移植在促进上皮伤口愈合，减少基质炎症，瘢痕形成和不需要的新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R01 EY06819的支持下，PI收集了足够的实验室和临床前兔数据，以支持这样的假设，即这种保存的羊膜也是恢复角膜缘上皮干细胞成功离体扩增所必需的“基质生态位”的理想基质。主要研究者已获得美国食品药品监督管理局（FDA）的IND（No.10313）和IRB批准，通过开展I期临床试验将上述基础研究转化为临床应用，以实现以下两个目的： 目的1：证实自体体外扩增角膜缘上皮干细胞用于治疗角膜移植的安全性和有效性。 单侧角膜缘干细胞缺乏的角膜表面重建。 目的2：确认同种异体体外扩增角膜缘上皮干细胞用于治疗角膜移植的安全性和有效性。 重建双侧角膜缘干细胞缺乏的角膜表面。 这项临床试验的完成将首次证明，上述新的手术技术可以用于缓解症状，并恢复视力的患者遭受的角膜缘干细胞缺乏症。随着后续临床试验的进一步修改和改进，这项新技术可能会开发成商业产品（FDA分类为“生物制品”）。此外，从基于FDA的cGMP指南的离体操作的这种平台，未来还可以通过靶向扩增的角膜缘上皮干细胞的基因疗法来开发新的治疗剂。

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.