TRANSPLANTATION OF EXPANDED LIMBAL EPITHELIAL STEM CELLS

扩增的角膜缘上皮干细胞移植

• 批准号: 6804225
• 负责人: SCHEFFER CG TSENG
• 金额: $ 29.34万
• 依托单位: TISSUETECH, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6804225
• 关键词: amnion; autologous transplantation; clinical research; clinical trial phase I; cornea disorder; corneal epithelium; cryopreservation; homologous transplantation; human subject; human therapy evaluation; stem cell transplantation; tissue engineering; wound healing

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.

描述（由申请人提供）：表现出角膜缘干细胞缺陷的角膜疾病仍然是临床医生处理最困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，多项研究表明羊膜移植可有效促进上皮伤口愈合，并减少间质炎症、疤痕和不必要的新血管形成。用于眼表重建的羊膜移植已获得 FDA 和 Medicare 的批准。在 RO1 EY06819 的支持下，PI 收集了足够的实验室和临床前兔子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”的理想基质，这对角膜缘上皮干细胞的成功离体扩增至关重要。 PI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，以实现以下两个目标： 目标 1：确认自体离体扩增角膜缘上皮干细胞用于治疗的安全性和有效性 重建单侧角膜缘干细胞完全缺乏的角膜表面。 目标 2：确认同种异体离体扩增的角膜缘上皮干细胞的安全性和有效性 重建双侧完全角膜缘干细胞缺陷的角膜表面。 这项临床试验的完成将首次证明上述新手术技术可用于缓解角膜缘干细胞完全缺乏症患者的症状并恢复视力。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“生物制剂”）。此外，基于FDA cGMP指南的离体操作平台，未来还可能通过针对扩增的角膜缘上皮干细胞的基因疗法开发新的治疗方法。