内皮祖细胞移植在糖尿病视网膜病变中的应用现状及挑战

Application studies and challenges of endothelial progenitor cells transplantation for diabetes retinopathy

内皮祖细胞(EPCs)是具有血管生成潜能的祖细胞,其主要功能一方面是通过旁分泌促血管生成因子及神经保护因子而发挥作用,另外一方面是具有向血管内皮细胞分化的能力,并将自身整合到新形成的毛细血管中,因而在血管修复和神经保护中发挥重要作用。EPCs的表面标志物和功能研究是EPCs研究的基础。目前一系列临床试验、动物实验和离体细胞学研究表明,EPCs的自体移植或与其他细胞联合移植可促进视网膜血管修复,改善视网膜功能且安全性较好。糖尿病视网膜病变(DR)被定义为由全身代谢异常引起的视网膜神经血管单位(NVU)受损的难治性视网膜疾病,EPCs数目改变及功能受损参与DR的发生和发展,眼科医师应该关注基于EPCs的疗法对DR的治疗意义。目前DR的治疗策略包括EPCs移植、EPCs与其他细胞联合移植以及内源性EPCs的调节,EPCs独特的生物学特性为其在修复NVU损伤及DR防治方面提供许多可能性。本文从EPCs的起源、生理病理状态、功能、治疗策略、临床应用5个方面展开,介绍EPCs在DR中的最新研究进展,同时对EPCs治疗存在的问题和技术瓶颈进行讨论。

Endothelial progenitor cells(EPCs)are progenitor cells possessing vasculogenic potential.The main function of EPCs is to play a role by paracrine angiogenic factors and neuroprotective factors.EPCs also have the ability to differentiate into endothelial cells and integrate themselves into newly formed capillaries.Therefore,EPCs play an important role in vascular repair and neuroprotection.The research on surface markers and functions of EPCs is the basis of EPCs research.A series of clinical trials,animal and cell experiments show that EPCs transplantation and joint transplantation of EPCs and other cells can promote vascular repair and improve retinal function with good safety.EPCs are expected to be an effective treatment for diabetic retinopathy(DR).DR is now defined as a refractory eye disease with retinal neurovascular unit(NVU)injury associated with systemic metabolism anbormality.Change in EPCs count and damage of EPCs function are involved in the occurrence and development of DR.Ophthalmologists should pay attention to the early managing approach of EPCs.Current treatment strategies include transplantation of EPCs,joint transplantation of EPCs with other cells,and regulation of endogenous EPCs.The unique biological characteristics of EPCs provide many possibilities in repairing retinal NVU injury and DR prevention and treatment.This article introduces the latest research progress of EPCs for DR from five aspects including the origin of EPCs,physiological and pathological state,function,treatment strategy and clinical application.At the same time,the existing problems and technical bottlenecks will also be discussed.