共查询到20条相似文献,搜索用时 15 毫秒
1.
视网膜色素上皮(RPE)对视觉功能的维持起着至关重要的作用。视网膜变性是全球不可治愈性致盲疾病的重要原因,它由视网膜色素上皮功能失常所引起。因此,视网膜色素上皮移植是视网膜变性患者恢复视力的一种最有前景的手段之一。随着干细胞技术的快速发展,从多能干细胞(PSC)到有功能的视网膜色素上皮细胞的体外分化诱导技术已经成熟,其中包括胚胎干细胞(ESCs)和诱导多能干细胞(iPSCs)等。此外,从患者特异性iPSCs分化而来的RPE更能用于阐明发病机理并有针对性地个体治疗。更值得一提的是,经诱导得到RPE的移植不论在动物模型中,还是在临床试验里都已经得到了可喜的治疗效果。本文回顾PSC来源RPE干预治疗视网膜变性的最新研究进展。 相似文献
2.
A major cause for vision impairment and blindness in industrialized countries is the loss of the light-sensing retinal tissue in the eye. Photoreceptor damage is one of the main characteristics found in retinal degeneration diseases, such as Retinitis Pigmentosa or age-related macular degeneration. The lack of effective therapies to stop photoreceptor loss together with the absence of significant intrinsic regeneration in the human retina converts such degenerative diseases into permanent conditions that are currently irreversible. Cell replacement by means of photoreceptor transplantation has been proposed as a potential approach to tackle cell loss in the retina. Since the first attempt of photoreceptor transplantation in humans, about twenty years ago, several research groups have focused in the development and improvement of technologies necessary to bring cell transplantation for retinal degeneration diseases to reality. Progress in recent years in the generation of human tissue derived from pluripotent stem cells (PSCs) has significantly improved our tools to study human development and disease in the dish. Particularly the availability of 3D culture systems for the generation of PSC-derived organoids, including the human retina, has dramatically increased access to human material for basic and medical research. In this review, we focus on important milestones towards the generation of transplantable photoreceptor precursors from PSC-derived retinal organoids and discuss recent pre-clinical transplantation studies using organoid-derived photoreceptors in context to related in vivo work using primary photoreceptors as donor material. Additionally, we summarize remaining challenges for developing photoreceptor transplantation towards clinical application. 相似文献
3.
Background
Transplantation as a therapeutic strategy for inherited retinal degeneration has been historically viewed to restore vision as a method by replacing the lost retinal cells and attempting to reconstruct the neural circuitry with stem cells, progenitor cells and mature neural retinal cells.Methods and Findings
We present evidence for an alternative strategy aimed at preventing the secondary loss of cones, the most crucial photoreceptors for vision, by transplanting normal photoreceptors cells into the eye of the P23H rat, a model of dominant retinitis pigmentosa. We carried out transplantation of photoreceptors or total neural retina in 3-month-old P23H rats and evaluated the function and cell counts 6 months after surgery. In both groups, cone loss was significantly reduced (10%) in the transplanted eyes where the cone outer segments were found to be considerably longer. This morphological effect correlated with maintenance of the visual function of cones as scored by photopic ERG recording, but more precisely with an increase in the photopic b-wave amplitudes by 100% and 78% for photoreceptor transplantation and whole retinal transplantation respectively.Conclusions
We demonstrate here that the transplanted tissue prevents the loss of cone function, which is further translated into cone survival. 相似文献4.
Hirofumi Uyama Michiko Mandai Masayo Takahashi 《Development, growth & differentiation》2021,63(1):59-71
Various advances have been made in the treatment of retinal diseases, including new treatment strategies and innovations in surgical devices. However, the treatment of degenerative retinal diseases, such as retinitis pigmentosa (RP) and age‐related macular degeneration (AMD), continues to pose a significant challenge. In this review, we focus on the use of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) to treat retinal diseases by harnessing the ability of stem cells to differentiate into different body tissues. The retina is a tissue specialized for light sensing, and its degradation leads to vision loss. As part of the central nervous system, the retina has very low regenerative capability, and therefore, treatment options are limited once it degenerates. Nevertheless, innovations in methods to induce the generation of retinal cells and tissues from ESCs/iPSCs enable the development of novel approaches for these irreversible diseases. Here we review some historical background and current clinical trials involving the use of stem‐cell‐derived retinal pigment epithelial cells for AMD treatment and stem cell‐derived retinal cells/tissues for RP therapy. Finally, we discuss our future vision of regenerative treatment for retinal diseases with a partial focus on our studies and introduce other interesting approaches for restoring vision. 相似文献
5.
Katherine J. Wert Jessica M. Skeie Richard J. Davis Stephen H. Tsang Vinit B. Mahajan 《Journal of visualized experiments : JoVE》2012,(69)
The loss of sight affects approximately 3.4 million people in the United States and is expected to increase in the upcoming years.1 Recently, gene therapy and stem cell transplantations have become key therapeutic tools for treating blindness resulting from retinal degenerative diseases. Several forms of autologous transplantation for age-related macular degeneration (AMD), such as iris pigment epithelial cell transplantation, have generated encouraging results, and human clinical trials have begun for other forms of gene and stem cell therapies.2 These include RPE65 gene replacement therapy in patients with Leber''s congenital amaurosis and an RPE cell transplantation using human embryonic stem (ES) cells in Stargardt''s disease.3-4 Now that there are gene therapy vectors and stem cells available for treating patients with retinal diseases, it is important to verify these potential therapies in animal models before applying them in human studies. The mouse has become an important scientific model for testing the therapeutic efficacy of gene therapy vectors and stem cell transplantation in the eye.5-8 In this video article, we present a technique to inject gene therapy vectors or stem cells into the subretinal space of the mouse eye while minimizing damage to the surrounding tissue. 相似文献
6.
Mike O. Karl 《Cell and tissue research》2013,353(2):311-325
Stem cell research offers a wide variety of approaches for the advancement of our understanding of basic mechanisms of neurodegeneration and tissue regeneration and for the discovery and development of new therapeutic strategies to prevent and restore neuronal cell loss. Similar to most other regions of our central nervous system, degenerative diseases of the retina lead to the loss of neurons, which are not replaced. Recent work in animals has provided proof-of-concept evidence for the restoration of photoreceptor cells by cell transplantation and neuronal cell replacement by regeneration from endogenous cell sources. However, efficient therapeutic prevention of neuronal cell loss has not been achieved. Moreover, successful cell replacement of retinal neurons in humans, including that of ganglion cells, remains a major challenge. Future successes in the discovery and translation of neuroprotective drug and gene therapies and of cell-based regenerative therapies will depend on a better understanding of the underlying disease pathomechanisms. Existing stem cell and cell-reprogramming technologies offer the potential to generate human retina cells, to develop specific human-cell-based retina disease models, and to open up novel therapeutic strategies. Further, we might glean substantial knowledge from species that can or cannot regenerate their neuronal retina, in the search for new therapeutic approaches. Thus, stem cell research will pave the way toward clinical translation. In this review, I address some of the major possibilities presently on offer and speculate about the power of stem cell research to gain further insights into the pathomechanisms of retinal neurodegeneration (with special emphasis on glaucoma) and to advance our therapeutic options. 相似文献
7.
The relevance of retinal diseases, both in society’s economy and in the quality of people’s life who suffer with them, has made stem cell therapy an interesting topic forresearch. Embryonic stem cells(ESCs), induced pluripotent stem cells(i PSCs) and adipose derived mesenchymal stem cells(ADMSCs) are the focus in current endeavors as a source of different retinal cells, such as photoreceptors and retinal pigment epithelial cells. The aim is to apply them for cell replacement as an option for treating retinal diseases which so far are untreatable in their advanced stage. ESCs, despite the great potential for differentiation, have the dangerous risk of teratoma formation as well as ethical issues, which must be resolved before starting a clinical trial. i PSCs, like ESCs, are able to differentiate in to several types of retinal cells. However, the process to get them for personalized cell therapy has a high cost in terms of time and money. Researchers are working to resolve this since i PSCs seem to be a realistic option for treating retinal diseases. ADMSCs have the advantage that the procedures to obtain them are easier. Despite advancements in stem cell application, there are still several challenges that need to be overcome before transferring the research results to clinical application. This paper reviews recent research achievements of the applications of these three types of stem cells as well as clinical trials currently based on them. 相似文献
8.
9.
Visual impairment severely affects the quality of life of patients and their families and is also associated with a deep economic impact. The most common pathologies responsible for visual impairment and legally defined blindness in developed countries include age-related macular degeneration, glaucoma and diabetic retinopathy. These conditions share common pathophysiological features: dysfunction and loss of retinal neurons. To date, two main approaches are being taken to develop putative therapeutic strategies: neuroprotection and cell replacement. Cell replacement is a novel therapeutic approach to restore visual capabilities to the degenerated adult neural retina and represents an emerging field of regenerative neurotherapy. The discovery of a population of proliferative cells in the mammalian retina has raised the possibility of harnessing endogenous retinal stem cells to elicit retinal repair. Furthermore, the development of suitable protocols for the reprogramming of differentiated somatic cells to a pluripotent state further increases the therapeutic potential of stem-cell-based technologies for the treatment of major retinal diseases. Stem-cell transplantation in animal models has been most effectively used for the replacement of photoreceptors, although this therapeutic approach is also being used for inner retinal pathologies. In this review, we discuss recent advances in the development of cell-replacement approaches for the treatment of currently incurable degenerative retinal diseases. 相似文献
10.
Degenerative retinal diseases affect millions of people worldwide, which can lead to the loss of vision. However, therapeutic approaches that can reverse this process are limited. Recent efforts have allowed the possibility of the stem cell-based regeneration of retinal cells and repair of injured retinal tissues. Although the direct differentiation of pluripotent stem cells into terminally differentiated photoreceptor cells comprises one approach, a series of studies revealed the intrinsic regenerative potential of the retina using endogenous retinal stem cells. Muller glial cells, ciliary pigment epithelial cells, and retinal pigment epithelial cells are candidates for such retinal stem cells that can differentiate into multiple types of retinal cells and be integrated into injured or developing retina. In this review, we explore our current understanding of the cellular identity of these candidate retinal stem cells and their therapeutic potential for cell therapy against degenerative retinal diseases. [BMB Reports 2015; 48(4): 193-199] 相似文献
11.
Olga L German Harmonie Vallese-Maurizi Tamara B Soto Nora P Rotstein Luis Enrique Politi 《World journal of stem cells》2021,13(10):1446-1479
Retinal degeneration is a major contributor to visual dysfunction worldwide. Although it comprises several eye diseases, loss of retinal pigment epithelial (RPE) and photoreceptor cells are the major contributors to their pathogenesis. Early therapies included diverse treatments, such as provision of anti-vascular endothelial growth factor and many survival and trophic factors that, in some cases, slow down the progression of the degeneration, but do not effectively prevent it. The finding of stem cells (SC) in the eye has led to the proposal of cell replacement strategies for retina degeneration. Therapies using different types of SC, such as retinal progenitor cells (RPCs), embryonic SC, pluripotent SCs (PSCs), induced PSCs (iPSCs), and mesenchymal stromal cells, capable of self-renewal and of differentiating into multiple cell types, have gained ample support. Numerous preclinical studies have assessed transplantation of SC in animal models, with encouraging results. The aim of this work is to revise the different preclinical and clinical approaches, analyzing the SC type used, their efficacy, safety, cell attachment and integration, absence of tumor formation and immunorejection, in order to establish which were the most relevant and successful. In addition, we examine the questions and concerns still open in the field. The data demonstrate the existence of two main approaches, aimed at replacing either RPE cells or photoreceptors. Emerging evidence suggests that RPCs and iPSC are the best candidates, presenting no ethical concerns and a low risk of immunorejection. Clinical trials have already supported the safety and efficacy of SC treatments. Serious concerns are pending, such as the risk of tumor formation, lack of attachment or integration of transplanted cells into host retinas, immunorejection, cell death, and also ethical. However, the amazing progress in the field in the last few years makes it possible to envisage safe and effective treatments to restore vision loss in a near future. 相似文献
12.
Retinal degeneration due to genetic, diabetic and age-related disease is the most common cause of blindness in the developed world. Blindness occurs through the loss of the light-sensing photoreceptors; to restore vision, it would be necessary to introduce alternative photosensitive components into the eye. The recent development of an electronic prosthesis placed beneath the severely diseased retina has shown that subretinal stimulation may restore some visual function in blind patients. This proves that residual retinal circuits can be reawakened after photoreceptor loss and defines a goal for stem-cell-based therapy to replace photoreceptors. Advances in reprogramming adult cells have shown how it may be possible to generate autologous stem cells for transplantation without the need for an embryo donor. The recent success in culturing a whole optic cup in vitro has shown how large numbers of photoreceptors might be generated from embryonic stem cells. Taken together, these threads of discovery provide the basis for optimism for the development of a stem-cell-based strategy for the treatment of retinal blindness. 相似文献
13.
Yao Li Yi-Ting Tsai Chun-Wei Hsu Deniz Erol Jin Yang Wen-Hsuan Wu Richard J Davis Dieter Egli Stephen H Tsang 《Molecular medicine (Cambridge, Mass.)》2012,18(1):1312-1319
The U.S. Food and Drug Administration recently approved phase I/II clinical trials for embryonic stem (ES) cell–based retinal pigmented epithelium (RPE) transplantation, but this allograft transplantation requires lifelong immunosuppressive therapy. Autografts from patient-specific induced pluripotent stem (iPS) cells offer an alternative solution to this problem. However, more data are required to establish the safety and efficacy of iPS transplantation in animal models before moving iPS therapy into clinical trials. This study examines the efficacy of iPS transplantation in restoring functional vision in Rpe65rd12/Rpe65rd12 mice, a clinically relevant model of retinitis pigmentosa (RP). Human iPS cells were differentiated into morphologically and functionally RPE-like tissue. Quantitative real-time polymerase chain reaction (RT-PCR) and immunoblots confirmed RPE fate. The iPS-derived RPE cells were injected into the subretinal space of Rpe65rd12/Rpe65rd12 mice at 2 d postnatally. After transplantation, the long-term surviving iPS-derived RPE graft colocalized with the host native RPE cells and assimilated into the host retina without disruption. None of the mice receiving transplants developed tumors over their lifetimes. Furthermore, electroretinogram, a standard method for measuring efficacy in human trials, demonstrated improved visual function in recipients over the lifetime of this RP mouse model. Our study provides the first direct evidence of functional recovery in a clinically relevant model of retinal degeneration using iPS transplantation and supports the feasibility of autologous iPS cell transplantation for retinal and macular degenerations featuring significant RPE loss. 相似文献
14.
José Mauricio Garcia Luisa Mendon?a Rodrigo Brant Murilo Abud Caio Regatieri Bruno Diniz 《World journal of stem cells》2015,7(1):160-164
In this review, we discuss about current knowledge about stem cell(SC) therapy in the treatment of retinal degeneration. Both human embryonic stem cell and induced pluripotent stem cell has been growth in culture for a long time, and started to be explored in the treatment of blinding conditions. The Food and Drug Administration, recently, has granted clinical trials using SC retinal therapy to treat complex disorders, as Stargardt’s dystrophy, and patients with geographic atrophy, providing good outcomes. This study ’s intent is to overview the critical regeneration of the subretinal anatomy through retinal pigment epithelium transplantation, with the goal of reestablish important pathways from the retina to the occipital cortex of the brain, as well as the differentiation from pluripotent quiescent SC to adult retina, and its relationship with a primary retinal injury, different techniques of transplantation, management of immune rejection and tumorigenicity, its potential application in improving patients’ vision, and, finally, approaching future directions and challenges for the treatment of several conditions. 相似文献
15.
视网膜退行性病变影响着全世界数百万人。然而,视网膜是人体再生能力很差的一类组织,成年机体无法自我更新那些病变中丢失的视网膜细胞,导致视网膜退行性病变的不可逆性。因此,恢复患者视觉将依赖于引入外源细胞替代丢失的视网膜神经元。胚胎干细胞(ES细胞)具有无限的自我更新能力和形成机体所有类型细胞的巨大分化潜力。这两个特性使得ES细胞成为细胞替代疗法的理想供体细胞。近年来,人们在探索将ES和诱导多能干细胞(iPS细胞)体外定向诱导分化为视网膜神经元,甚至整个视网膜方面已取得多项进展,并且体外形成的视网膜细胞可以与宿主视网膜整合。在此篇综述中,首先简要概括哺乳动物视网膜的组织结构、发育过程和调控机制,然后,重点阐述近年来科研工作者探索ES/iPS细胞体外诱导分化为视网膜细胞和组织的研究进展。 相似文献
16.
17.
Shaomei Wang Bin Lu Sergei Girman Jie Duan Trevor McFarland Qing-shuo Zhang Markus Grompe Grazyna Adamus Binoy Appukuttan Raymond Lund 《PloS one》2010,5(2)
Background
Retinitis pigmentosa (RP) is characterized by progressive night blindness, visual field loss, altered vascular permeability and loss of central vision. Currently there is no effective treatment available except gene replacement therapy has shown promise in a few patients with specific gene defects. There is an urgent need to develop therapies that offer generic neuro-and vascular-protective effects with non-invasive intervention. Here we explored the potential of systemic administration of pluripotent bone marrow-derived mesenchymal stem cells (MSCs) to rescue vision and associated vascular pathology in the Royal College Surgeons (RCS) rat, a well-established animal model for RP.Methodology/Principal Findings
Animals received syngeneic MSCs (1×106 cells) by tail vein at an age before major photoreceptor loss. Principal results: both rod and cone photoreceptors were preserved (5–6 cells thick) at the time when control animal has a single layer of photoreceptors remained; Visual function was significantly preserved compared with controls as determined by visual acuity and luminance threshold recording from the superior colliculus; The number of pathological vascular complexes (abnormal vessels associated with migrating pigment epithelium cells) and area of vascular leakage that would ordinarily develop were dramatically reduced; Semi-quantitative RT-PCR analysis indicated there was upregulation of growth factors and immunohistochemistry revealed that there was an increase in neurotrophic factors within eyes of animals that received MSCs.Conclusions/Significance
These results underscore the potential application of MSCs in treating retinal degeneration. The advantages of this non-invasive cell-based therapy are: cells are easily isolated and can be expanded in large quantity for autologous graft; hypoimmunogenic nature as allogeneic donors; less controversial in nature than other stem cells; can be readministered with minor discomfort. Therefore, MSCs may prove to be the ideal cell source for auto-cell therapy for retinal degeneration and other ocular vascular diseases. 相似文献18.
Yichi Zhang Yan Luo Kaijing Li Min Zhang Bing Huang Yuting Peng Wenchong Wang Weihua Li Yizhi Liu 《Cytotherapy》2013,15(11):1416-1425
Background aimsRecent advances in stem cell research have raised the possibility of stem cells repairing or replacing retinal photoreceptor cells that are either dysfunctional or lost in many retinal diseases. Various types of stem cells have been used to replace retinal photoreceptor cells. Recently, peripheral blood stem cells, a small proportion of pluripotent stem cells, have been reported to mainly exist in the peripheral blood mononuclear cells (PBMCs).MethodsIn this study, the effects of pre-induced adult human PBMCs (hPBMCs) on the degenerative retinas of rd1 mice were investigated. Freshly isolated adult hPBMCs were pre-induced with the use of the conditioned medium of rat retinas for 4 days and were then labeled with chloromethyl-benzamidodialkylcarbocyanine (CM-DiI) and then transplanted into the subretinal space of the right eye of rd1 mice through a trans-scleral approach. The right eyes were collected 30 days after transplantation. The survival and migration of the transplanted cells in host retinas were investigated by whole-mount retinas, retinal frozen sections and immunofluorescent staining.ResultsAfter subretinal transplantation, pre-induced hPBMCs were able to survive and widely migrate into the retinas of rd1 mice. A few CM-DiI–labeled cells migrated into the inner nuclear layer and the retinal ganglion cell layer. Some transplanted cells in the subretinal space of rd1 host mice expressed the human photoreceptor–specific marker rhodopsin.ConclusionsThis study suggests that pre-induced hPBMCs may be a potential cell source of cell replacement therapy for retinal degenerative diseases. 相似文献
19.
Neural stem cells for spinal cord repair 总被引:1,自引:0,他引:1
Sandner B Prang P Rivera FJ Aigner L Blesch A Weidner N 《Cell and tissue research》2012,349(1):349-362
Spinal cord injury (SCI) causes the irreversible loss of spinal cord parenchyma including astroglia, oligodendroglia and neurons. In particular, severe injuries can lead to an almost complete neural cell loss at the lesion site and structural and functional recovery might only be accomplished by appropriate cell and tissue replacement. Stem cells have the capacity to differentiate into all relevant neural cell types necessary to replace degenerated spinal cord tissue and can now be obtained from virtually any stage of development. Within the last two decades, many in vivo studies in small animal models of SCI have demonstrated that stem cell transplantation can promote morphological and, in some cases, functional recovery via various mechanisms including remyelination, axon growth and regeneration, or neuronal replacement. However, only two well-documented neural-stem-cell-based transplantation strategies have moved to phase I clinical trials to date. This review aims to provide an overview about the current status of preclinical and clinical neural stem cell transplantation and discusses future perspectives in the field. 相似文献
20.
Survival and differentiation of cultured retinal progenitors transplanted in the subretinal space of the rat 总被引:34,自引:0,他引:34
Chacko DM Rogers JA Turner JE Ahmad I 《Biochemical and biophysical research communications》2000,268(3):842-846
We have shown that embryonic retina contains progenitors which display stem cell properties in vitro. These cells are proliferative and in addition to expressing the neuroectodermal marker, nestin, are multipotential. These properties and the fact that the putative stem cells can differentiate as photoreceptors when exposed to conducive environment identify them as a viable transplantation reagents to address degenerative retinal diseases. Here we report the survival and differentiation of cultured retinal progenitors upon subretinal transplantation. The retinal progenitor grafts, either as neural spheres or in the form of dissociated cells, survived without disrupting the morphology and laminar organization of the host retina. They did not form rosettes, the morphological barrier to the reconstruction of the normal anatomy of the retina. In addition, transplanted progenitors expressed photoreceptor-specific markers, suggesting that progenitors have the potential to differentiate as photoreceptors. Our observations suggest that cultured retinal progenitors can be a viable reagents for therapeutic transplantation. 相似文献