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和最具挑战性的疾病之一。自1995年PI重新引入保存的人羊膜移植用于眼表重建以来，大量研究表明羊膜移植可有效促进上皮伤口愈合，减少间质炎症、瘢痕形成和不必要的新血管形成。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兔数据来支持这样的假设，即这种保存的羊膜也是恢复“基质生态位”的理想底物，而“基质生态位”对于成功地体外扩增角膜缘上皮干细胞至关重要。PI已获得美国食品和药物管理局（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，以实现以下两个目标：

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.