干细胞移植治疗视网膜变性疾病的研究进展

视网膜变性疾病是一类与遗传相关的变性疾病,导致患者渐进性视觉丢失,是主要的致盲性眼病之一,其共同病理基础是视网膜光感受器细胞的变性、坏死和凋亡,然而目前尚无有效的治疗方法。细胞移植治疗是目前实验研究治疗视网膜变性疾病的主要方法之一。近年研究表明将感光前体细胞或视网膜色素上皮细胞移植到视网膜下腔或玻璃体内,可以延缓宿主感光细胞的凋亡、替代凋亡的感光细胞、挽救残存的视觉功能和修复视网膜结构。细胞移植治疗的一个很重要的问题是移植细胞的来源问题,目前主要的移植细胞来源是视网膜祖／干细胞、胚胎干细胞和诱导多潜能干细胞等。本文就干细胞移植治疗视网膜变性疾病的研究进展进行综述。     

胚胎干细胞诱导分化视网膜细胞的方法新进展

视网膜变性疾病是引起视力丧失的重要原因,由于这类眼病的病因不明确、发病机制复杂,目前尚无有效的治疗方法.近年来,干细胞研究领域取得了突破性进展,干细胞具有分化为机体所有细胞的潜能,可以利用胚胎干细胞(ESCs)分化出各种视网膜细胞,这为视网膜变性疾病的治疗带来了新的曙光.ESCs治疗视网膜变性疾病至关重要的一步是将ESCs分化为视网膜光感受器细胞和视网膜色素上皮(RPE)样细胞.本文对自发诱导培养法、共培养法、细胞因子诱导法、单层贴壁诱导培养法和3D诱导培养法等ESCs分化为视网膜光感受器细胞和RPE细胞方法的最新进展进行综述.     

视网膜色素上皮细胞的诱导分化及其移植治疗方法的研究进展

视网膜色素上皮(retinal pigment epithelium,RPE)的病变可以导致多种视网膜疾病,目前缺乏有效的治疗手段.人类多能干细胞具有多向分化潜能,为此类疾病的细胞治疗提供了理想来源.本文将近年来胚胎干细胞和诱导多能干细胞体外定向分化为RPE细胞及移植治疗年龄相关性黄斑变性等视网膜疾病的研究进行了综述.     

视网膜色素上皮细胞的诱导分化及其移植治疗方法的研究进展

视网膜色素上皮(retinal pigment epithelium,RPE)的病变可以导致多种视网膜疾病,目前缺乏有效的治疗手段.人类多能干细胞具有多向分化潜能,为此类疾病的细胞治疗提供了理想来源.本文将近年来胚胎干细胞和诱导多能干细胞体外定向分化为RPE细胞及移植治疗年龄相关性黄斑变性等视网膜疾病的研究进行了综述.     

诱导多能干细胞在视网膜疾病研究中的应用

诱导多能干细胞(induced pluripotent stem cells,iPSCs)是成体细胞通过重编程而获得的一类具有胚胎干细胞相似特性和功能的细胞.近年来,iPSCs在再生医学和干细胞研究领域备受关注,尤其是患者特异源性iPSCs,来源方便、无免疫排斥和伦理学问题,同时还可以保留特定个体基因型,为再生医学以及细胞移植疗法提供了新的细胞来源.目前,iPSCs在视网膜疾病研究领域取得了长足的进步.本文主要对iPSCs向视网膜色素上皮细胞、感光细胞和神经节细胞的诱导分化及细胞移植研究、安全性评价等方面进行综述,探讨iPSCs在视网膜疾病研究中的应用和前景.     

干细胞移植在眼科的应用前景

干细胞具有自我更新、高度增殖及多向分化潜能的优点,主要分为胚胎干细胞和成体干细胞。胚胎干细胞移植在眼科的应用尚处于实验研究阶段,其在视网膜变性疾病及视神经病变治疗中的应用潜能渐成为研究的热点。越来越多的动物实验表明成体干细胞具有横向分化潜能,其自身的应用优势为难治性眼科疾病的治疗提供了新的途径。本文就干细胞移植在眼科应用的前景作一综述。     

干细胞在视网膜退行性疾病中的应用新进展

视网膜退行性疾病,如年龄相关性黄斑变性、视网膜色素变性、青光眼视神经萎缩等,是以视神经细胞、感光细胞及视网膜色素细胞等退行性变为主要特征的一类疾病,是目前主要的致盲性眼病,一直以来都认为成熟哺乳动物视网膜细胞缺乏有效的自我修复及再生能力,因此视网膜细胞凋亡具有不可逆性,目前还缺乏有效的促进视网膜再生方法,而干细胞以其独有的具有向目的细胞分化增殖,以取代变性、凋亡细胞的生物学特性,可作为一种替代疗法,为视网膜细胞的再生、恢复视功能提供了新的思路.本文从视网膜干细胞的来源及其在视网膜退行性疾病的应用进行综述.     

干细胞移植在眼科的应用前景

干细胞具有自我更新、高度增殖及多向分化潜能的优点，主要分为胚胎干细胞和成体干细胞。胚胎干细胞移植在眼科的应用尚处于实验研究阶段，其在视网膜变性疾病及视神经病变治疗中的应用潜能渐成为研究的热点。越来越多的动物实验表明成体干细胞具有横向分化潜能，其自身的应用优势为难治性眼科疾病的治疗提供了新的途径。本就干细胞移植在眼科应用的前景作一综述。     

视网膜修复中干细胞的应用

视网膜疾病由于其不可逆转的致盲性而影响人类生存质量.随着对干细胞研究的深入,基于干细胞移植的细胞替代疗法为视网膜疾病的治疗开辟了新的途径.近年来眼组织来源的视网膜干细胞或祖细胞、非眼组织来源的间充质干细胞、造血干细胞、神经干细胞、胚胎干细胞以及诱导多能干细胞在视网膜损伤疾病中的应用取得了很多突破性进展,它们不仅可以被诱导分化为各种视网膜神经元细胞、胶质细胞,而且移植到体内可以整合到损伤视网膜,甚至可以发挥正常视网膜神经元细胞功能.     

视网膜发育中的神经于细胞

视网膜作为脑组织的延伸，存在大量神经干细胞，在内外源性因子机制及各基因调节机制作用下，增殖分化为视网膜各型神经元及神经胶质细胞。应用无血清培养及单细胞克隆技术可分离培养出特异性表达nestin的视网膜干细胞。由于视网膜干细胞具备自我更新能力及多分化潜能，有望用于退行性神经疾病如：视网膜色素变性、老年黄斑变性、晚期青光眼等的细胞替代治疗或药物、基因治疗的载体。     

Current studies on induced pluripotent stem cells in retinal degenerative diseases

Retinal degeneration diseases are a group of severe eye diseases that can lead to blindness. They are characterized by degeneration and apoptosis of photoreceptor cells and still lacking effective therapeutic procedures. Pluripotent stem cells (induced pluripotent stem cells, iPS cells) obtained from somatic cell reprogramming are similar to the embryonic stem cells (embryonic stem cells, ES cells), which have unlimited proliferation, differentiation and memory characteristics. Retinal cells from iPS cells have been used in cell transplantation for the treatment of retinal diseases, for the study of pathogenesis and drug toxicity evaluation in retinal degenerative diseases. This may provide new ideas and novel procedures for the treatment of retinal degenerative diseases in the future.     

诱导多能干细胞在眼科的研究进展

2006年诱导多能干细胞(iPSCs)的建立被誉为是干细胞研究领域的重大突破,使得进行患者体细胞来源的干细胞治疗成为可能.近年的研究表明,动物和人的成纤维细胞、B淋巴细胞、神经干细胞、头发角质细胞、胰腺细胞、脐带基质和羊膜的间充质细胞均可重编程成为iPSCs并可通过一定的诱导分化为特定类型的细胞,为多种疾病的特异性治疗提供了新的方法.而iPSCs研究在眼科领域的研究也取得了长足进展.在眼科,iPSCs诱导后可分化为视网膜色素上皮(RPE)细胞、感光细胞和其他视网膜细胞,从而为治疗视 网膜退行性病变奠定了基础.与传统的干细胞治疗不同,iPSCs移植治疗相应的疾病避免了传统干细胞治疗 所存在的道德伦理及免疫排斥等限制,具有较好的应用前景.就iPSCs的概念、诱导策略及方法、在眼科领域的研究现状、研究中存在的问题及应用前景等方面进行综述.     

极小胚胎样干细胞的研究现状和眼科临床意义

极小胚胎样干细胞（ very small em yonic-like stem cells, VSELs）是美国路易斯维尔大学Kucia 研究小组从小鼠骨髓和人脐带血中分离出一种具有类似胚胎干细胞生物特性的多潜能成体干细胞。与胚胎干细胞相似的外表---细胞形态及表面标志、以及相似的内在---多分化潜能决定了VSELs一出现就被细胞替代疗法视为最有潜力的种子细胞,本文就VSELs的研究历程及在眼科干细胞治疗视网膜退行性疾病中的临床意义作一综述。     

组织工程在视网膜退行性疾病中的应用进展

视网膜退行性疾病的主要病理基础是视网膜各级神经元的结构和功能性异常,最终造成患者视力的不可逆性损害,目前缺乏有效的治疗方法。近年来干细胞替代治疗方法的出现为此类致盲性眼病的治疗带来了希望,其相关研究已取得一定的进展。但是在研究中发现,干细胞的眼部移植仍存在着一些难点,如移植后细胞的移行能力、存活效率以及向目的细胞的分化能力等。因此,最近研究显示,视网膜组织工程技术的研究和发展有助于解决或弥补以上问题。针对目前干细胞和组织工程视网膜的研究状况,对视网膜组织工程的种子细胞、支架材料、体内移植技术等研究进展、取得的成绩和存在的问题进行综述。     

Retinal stem cell transplantation: Balancing safety and potential

Stem cell transplantation holds great promise as a potential treatment for currently incurable retinal degenerative diseases that cause poor vision and blindness. Recently, safety data have emerged from several Phase I/II clinical trials of retinal stem cell transplantation. These clinical trials, usually run in partnership with academic institutions, are based on sound preclinical studies and are focused on patient safety. However, reports of serious adverse events arising from cell therapy in other poorly regulated centers have now emerged in the lay and scientific press. While progress in stem cell research for blindness has been greeted with great enthusiasm by patients, scientists, doctors and industry alike, these adverse events have raised concerns about the safety of retinal stem cell transplantation and whether patients are truly protected from undue harm. The aim of this review is to summarize and appraise the safety of human retinal stem cell transplantation in the context of its potential to be developed into an effective treatment for retinal degenerative diseases.     

诱导多能干细胞在眼科的研究进展

以视网膜神经元不可逆性损伤为病理基础的视网膜变性类疾病是目前主要的致盲性眼病之一,针对其神经损伤修复的药物治疗却十分有限.最新研究发现的诱导多能干细胞(iPSCs)是通过基因转染技术将转录因子导入动物或人的体细胞内,使体细胞直接重构成为胚胎干细胞样的多潜能细胞.由患者体细胞诱导的iPSCs不仅具有强大的自我更新和分化潜能,而且可避免以往胚胎干细胞存在的宿主排斥反应和伦理学限制等缺点,同时眼部屈光介质清晰的特点还使得自体干细胞移植治疗视网膜变性类疾病具有易于观察、便于操作的优势,相信会为这一难治性疾病的治疗开辟新的途径.对iPSCs的研究发展历程、iPSCs的特性和优势、iPSCs在眼科的诱导和定向分化能力进行综述.     

Embryonic stem cells: potential source for ocular repair

Many ocular diseases, such as retinitis pigmentosa and age-related macular degeneration, reflect damage to specific cells that are not normally repaired or replaced. Preliminary results of animal studies suggest that these degenerative diseases may be treatable by transplantation of healthy fetal cells. However, obtaining a sufficient number of suitable donor cells remains a problem. The isolation of human embryonic stem (ES) cells has drawn much attention because of their potential clinical application for patients with these degenerative diseases. Because ES cells have the potential to generate all adult cell types, ocular diseases resulting from the failure of specific cell types would be potentially treatable through the transplantation of differentiated cells derived from ES cells. In addition, because ES cells can proliferate indefinitely in their undifferentiated state, they are expected to alleviate the problem of the shortage of donor cells for cell-replacement therapy. Recently, reproducible and efficient differentiation methods for the generation of lens cells, retinal neurons, and retinal pigment epithelial (RPE) cells from ES cells have been developed. This review focuses especially on these ocular cells differentiated from ES cells. We will also discuss the potential therapeutic uses of ES cells for the treatment of ocular diseases.     

干细胞诱导分化为视网膜色素上皮细胞的途径探讨

近年来,干细胞在眼科领域的研究及应用受到高度关注,胚胎干细胞(ES)、成体干细胞能够被定向诱导分化成视网膜色素上皮细胞,由此可获得转分化的大量的视网膜色素上皮细胞源,通过体内干细胞及视网膜色素上皮细胞移植有望应用于各种视网膜退行性疾病的细胞替代治疗。本文就各种干细胞诱导分化为视网膜色素上皮细胞的途径及应用进行探讨。     

Gene-independent therapeutic interventions to maintain and restore light sensitivity in degenerating photoreceptors

Neurodegenerative retinal diseases are a prime cause of blindness in industrialized countries. In many cases, there are no therapeutic treatments, although they are essential to improve patients' quality of life. A set of disease-causing genes, which primarily affect photoreceptors, has already been identified and is of major interest for developing gene therapies. Nevertheless, depending on the nature and the state of the disease, gene-independent strategies are needed. Various strategies to halt disease progression or maintain function of the retina are under research. These therapeutic interventions include neuroprotection, direct reprogramming of affected photoreceptors, the application of non-coding RNAs, the generation of artificial photoreceptors by optogenetics and cell replacement strategies. During recent years, major breakthroughs have been made such as the first optogenetic application to a blind patient whose visual function partially recovered by targeting retinal ganglion cells. Also, RPE cell transplantation therapies are under clinical investigation and show great promise to improve visual function in blind patients. These cells are generated from human stem cells. Similar therapies for replacing photoreceptors are extensively tested in pre-clinical models. This marks just the start of promising new cures taking advantage of developments in the areas of genetic engineering, optogenetics, and stem-cell research. In this review, we present the recent therapeutic advances of gene-independent approaches that are currently under clinical evaluation. Our main focus is on photoreceptors as these sensory cells are highly vulnerable to degenerative diseases, and are crucial for light detection.     

Immunohistologic study of proliferative vitreoretinopathy

An immunohistologic study was performed on pars plana specimens obtained by biopsy in ten patients with rhegmatogenous retinal detachment, with or without proliferative vitreoretinopathy. Using immunofluorescence or immunoperoxidase procedures, linear deposits of IgG, IgA, and complement components were found in the eight cases of retinal detachment with proliferative vitreoretinopathy at the basal pole of the pigment epithelial cells and within the stroma. In contrast, these deposits were absent from the normal pars plana and from the retinal detachment without proliferative vitreoretinopathy. Moreover, pigment and nonpigment epithelial cells were found to express HLA-DR and HLA-DQ determinants in six of the eight patients with proliferative vitreoretinopathy. Our results are similar to those obtained in a previous study on proliferative diabetic retinopathy, which suggests the involvement of autoimmune phenomena in proliferative diseases and eventual interactions between the immune system and peptide growth factors. However, whether or not this immune reaction functions in the initiation or extension of intraocular proliferative syndromes remains to be determined.