Safety and Feasibility of Cultivated Autologous Limbal Epithelial Cell (CALEC) Transplantation in the Treatment of Limbal Stem Cell Deficiency

角膜缘上皮干细胞负责角膜上皮的更新。当这些细胞变成 一种称为角膜缘干细胞缺乏症(LSCD)的疾病会导致视力障碍 损伤和生活质量下降。LSCD在北美困扰着数以千计的患者。在患有 单侧LSCD，健康对侧眼角膜缘干细胞可用于角膜表面重建 一种称为自体结膜缘移植(CLU)的手术。尽管Clau在大多数情况下都是成功的 单侧LSCD，它作为供体角膜的两大块存在导致LSCD的潜在风险 传统上，角膜缘是为了这一过程而收获的。为了规避这种风险，最近有一种新技术 已经开发出所谓的培养的自体角膜缘上皮细胞(CALEC)移植。在这 技术，来自供体角膜缘的一小部分细胞在移植前在实验室中扩增以 治疗眼部病变，最大限度地降低对供体角膜的损伤风险。 由于在美国没有可用的CALEC产品，我们已经优化和标准化了 去除抗生素和小鼠饲养层细胞并采用重复性高的方法制备CALEC 用于细胞分离、扩增和合成的CALEC片材的质量控制。我们已经收到了调查报告 美国食品和药物管理局批准的新药申请(IND#16102)，允许我们的CALEC移植物在 马萨诸塞州波士顿马萨诸塞州眼耳医院(MEEI)，治疗单侧LSCD。 这是一项单中心研究，旨在评估CALEC移植物的安全性和可行性，并将其疗效与Clau进行比较。 24例单侧LSCD患者。研究设计已经得到FDA的批准。通过展示其安全性， CALEC的可行性和有效性，本研究为CALEC移植的广泛应用奠定了基础 在单侧LSCD患者中，通过与美国各地的其他机构共享该技术。 这是对之前提交的U-10拨款的重新提交。有三架UG-1合作机 协议包括主席赠款、协调中心赠款和资源中心赠款。在主席的座位上 Grant、Ula Jurkunas医学博士和Ahmad Kheirkhah医学博士是首席调查员，他们将负责 这项研究的总体进行以及提供科学、技术和行政领导。MEEI将 成为临床中心，负责招募和保留研究参与者和 执行研究议定书。协调中心赠款将由Jaeb卫生中心提交 研究，佛罗里达州坦帕，将提供科学、统计和方法领导，后勤 对研究的协调和支持。资源中心赠款将由康奈尔和奥莱利家庭提交 位于马萨诸塞州波士顿的达纳-法伯癌症研究所的细胞操纵核心设施(CMCF)，该公司将制造 CALEC移植物。一名NEI计划官员将参与这些合作协议，以协助 本研究各方面的首席调查员。

Limbal epithelial stem cells are responsible for renewal of the corneal epithelium. When these cells become dysfunctional or deficient, a disease called limbal stem cell deficiency (LSCD) develops which causes visual impairment and reduced quality of life. LSCD afflicts thousands of patients in North America. In patients with unilateral LSCD, limbal stem cells from the healthy fellow eye can be used for corneal surface reconstruction in a procedure called conjunctival limbal autograft (CLAU). Although CLAU is successful in majority of cases with unilateral LSCD, it carries the potential risk of causing LSCD in the donor cornea as two large pieces of the limbus are conventionally harvested for the procedure. To circumvent this risk, a new technique has recently been developed, so-called Cultivated Autologous Limbal Epithelial Cell (CALEC) transplantation. In this technique, cells from a small area of the donor limbus are expanded in the laboratory before transplantation to the diseased eye, minimizing the risk of damage to the donor cornea. As there is no CALEC product available in the U.S., we have optimized and standardized the techniques of CALEC preparation by removing antibiotics and murine feeder cells, and employing highly reproducible methods for cell isolation, expansion and quality control of the resultant CALEC sheets. We have received Investigational New Drug Application (IND #16102) approval from the FDA for our CALEC graft to perform a clinical trial at the Massachusetts Eye and Ear Infirmary (MEEI), Boston, MA, for unilateral LSCD. This is a single center study to assess safety and feasibility of CALEC grafts and to compare its efficacy to CLAU in 24 patients with unilateral LSCD. Study design has been approved by the FDA. By showing the safety, feasibility and efficacy of CALEC, this study will pave the way for widespread use of the CALEC transplantation in patients with unilateral LSCD by sharing the technology with other institutions across the U.S. This is a resubmission of a previously submitted U-10 grant. There are three companion UG-1 Cooperative Agreements including Chair’s Grant, Coordinating Center Grant, and Resource Center Grant. In the Chair’s Grant, Ula Jurkunas, MD, and Ahmad Kheirkhah, MD are the Principal Investigators who will be responsible for the overall conduct of this study and for providing scientific, technical, and administrative leadership. MEEI will be the Clinical Center which will be responsible for recruitment and retention of the study participants and implementation of the study protocol. Coordinating Center Grant will be submitted by Jaeb Center for Health Research, Tampa, FL, which will provide the scientific, statistical and methodological leadership, logistical coordination and support for the study. Resource Center Grant will be submitted by Connell and O’Reilly Families Cell Manipulation Core Facility (CMCF) at the Dana-Farber Cancer Institute, Boston, MA, which will manufacture the CALEC graft. An NEI Program Officer will be involved for these Cooperative Agreements to assist the Principal Investigators in all aspects of the study.