纳米磁珠连接Y-27632促人脐血内皮祖细胞修复角膜内皮缺损的研究

项目名称： 纳米磁珠连接Y-27632促人脐血内皮祖细胞修复角膜内皮缺损的研究

项目编号： No.81500765

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 邵春益

作者单位： 上海交通大学

项目金额： 18万元

中文摘要： 角膜内皮失代偿导致角膜混浊、视力下降甚至失明，角膜内皮移植是主要治疗方法，但角膜供体来源缺乏严重限制了该技术的开展。为了突破这个瓶颈，研究者们一直在寻找自体来源的干细胞替代角膜内皮细胞治疗角膜内皮失代偿疾病。我们前期研究发现，人脐血内皮祖细胞（EPC）能初步修复角膜内皮缺损，但在随访期内角膜未能完全恢复透明，预实验中发现小分子化合物Y-27632在体外能促进人脐血EPC向角膜内皮细胞分化。为进一步提高人脐血EPC修复角膜内皮缺损的效果，本项目以纳米磁珠为载体连接Y-27632，通过人脐血EPC吞噬磁珠，将Y-27632导入细胞内，再将细胞注射至兔前房，在体外磁场作用下，使人脐血EPC定向移动至角膜内皮缺损处，促进人脐血EPC向角膜内皮细胞分化，修复角膜内皮缺损。本项目的实施有望为角膜内皮失代偿疾病提供新的细胞来源，解决临床角膜供体来源缺乏的难题。

中文关键词： 移植；纳米磁珠；人脐血内皮祖细胞；Y-27632；组织再生

英文摘要： Fuchs’ dystrophy and bullous keratopathy are two common corneal endothelial diseases that involve progressive corneal edema and the loss of vision, and these diseases require corneal transplantation. However, the global shortage of donor corneas limits the transplantation. There is a great need to find new therapies to restore corneal clarity that is lost due to endothelial dysfunction. Using stem cells to repair corneal endothelium might resolve this problem. We have found the human umbilical cord blood endothelial progenitor cells (UCB EPC) had the possibility to repair corneal endothelium defect, but in the follow-up time the cornea failed to regain totally transparent. It has been reported that the ROCK inhibitor Y-27632 can facilitate corneal endothelial cells proliferation. We also found that Y-27632 could facilitate UCB EPC to different to cornea endothelial cells. In this study, Fluorescent magnetic nanoparticles (FMNPs) are conjugated with Y-27632. The UCB EPCs labeled with Y27632-FMNPs are transplanted into the rabbit anterior chamber combined with magnetic attraction, to repair corneal endothelium defect. The feasibility of this method is investigated. This study will provide a promising cell therapy for corneal endothelial dysfunction.

英文关键词： Transplantation;Nanoparticles;Umbilical cord blood endothelial progenitor cells;Y-27632;Tissue regeneration