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

培养自体角膜缘上皮细胞（CALEC）移植治疗角膜缘干细胞缺乏症的安全性和可行性

• 批准号: 9277781
• 负责人: Allison Renee Ayala
• 金额: $ 19.63万
• 依托单位: JAEB CENTER FOR HEALTH RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9277781
• 关键词: Adverse event; Alpha Cell; Antibiotics; Area; Autologous; Autologous Transplantation; Biological Preservation; Boston; Cell Separation; Cell Transplantation; Cells; Certification; Clinical; Clinical Trials; Communication; Companions; Core Facility; Cornea; Dana-Farber Cancer Institute; Data; Data Analyses; Data Collection; Data Coordinating Center; Databases; Development; Disease; Documentation; Ear; Epithelial; Epithelial Cells; Evaluation Studies; Eye; Eye diseases; FDA approved; Family; Feedback; Future; Grant; Harvest; Health; Human Resources; Institution; Institutional Review Boards; Investigational New Drug Application; Laboratories; Leadership; Logistics; Manuscripts; Massachusetts; Medical; Methodology; Methods; Monitor; Mus; North America; Online Systems; Participant; Patient Participation; Patients; Principal Investigator; Procedures; Process; Protocols documentation; Quality Control; Quality of life; Recruitment Activity; Reporting; Reproducibility; Research; Research Design; Research Infrastructure; Resolution; Resources; Risk; Role; Safety; Sample Size; Standardization; Statistical Data Interpretation; Stem cells; Surface; System; Techniques; Technology; Time; Time Study; TimeLine; Training; Transplantation; U-Series Cooperative Agreements; Visual impairment; base; cell preparation; corneal epithelium; data management; experience; limbal; novel; organizational structure; programs; quality assurance; reconstruction; risk minimization; safety and feasibility; safety study; standard care; web site

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.

边缘上皮干细胞负责更新角膜上皮。当这些细胞变成 功能失调或缺乏，一种称为缘干细胞缺乏症（LSCD）的疾病会导致视觉 损害和生活质量降低。 LSCD困扰着北美成千上万的患者。在患者中 来自健康同伴眼睛的单侧LSCD，膜缘干细胞可用于角膜表面重建 一种称为结膜缘自体移植（CLAU）的程序。尽管Clau在大多数情况下都成功 单侧LSCD，它具有引起捐赠者角膜LSCD的潜在风险 通常将边缘用于该过程。为了规避这种风险，最近有一种新技术 开发了所谓的自体缘上皮细胞（CALEC）移植。在这个 技术，来自捐赠者边缘小区域的细胞在移植到实验室中扩展 解散的眼睛最大程度地减少了对捐赠者角膜损害的风险。 由于美国没有CALEC产品，我们已经优化和标准化了的技术 CALEC制备通过去除抗生素和鼠喂食器细胞，并采用高度可重复的方法 用于细胞隔离，对所得CALEC纸的扩展和质量控制。我们收到了调查 FDA的新药应用（IND＃16102）批准我们的CALEC移植物在 马萨诸塞州波士顿的马萨诸塞州眼科医务室（MEEI），用于单方面LSCD。 这是一项单一的中心研究，用于评估CALEC图形的安全性和可行性并将其有效性与CLAU进行比较 在24例单侧LSCD患者中。研究设计已得到FDA的批准。通过显示安全性， CALEC的可行性和效率，这项研究将为宽度使用CALEC移植铺平道路 通过与美国其他机构共享该技术的单侧LSCD患者 这是先前提交的U-10赠款的重新提交。有三个合作伙伴UG-1合作社 协议，包括主席的赠款，协调中心赠款和资源中心赠款。在椅子上 格兰特，医学博士Ula Jurkunas和医学博士Ahmad Kheirkhah是主要调查员 这项研究的总体行为以及提供科学，技术和行政领导。 meei会 成为负责研究参与者招募和保留的临床中心 实施研究方案。协调中心赠款将由JAEB卫生中心提交 研究，坦帕，佛罗里达州，将提供科学，统计和方法论领导，后勤 对研究的协调和支持。资源中心赠款将由Connell和O’Reilly Family提交 马萨诸塞州波士顿Dana-Farber癌症研究所的细胞操纵核心设施（CMCF），该研究所将生产 库克移植物。 NEI计划官员将参与这些合作协议，以协助 研究的各个方面的主要研究人员。