German Olga L, Vallese-Maurizi Harmonie, Soto Tamara B, Rotstein Nora P, Politi Luis Enrique
Department of Biology, Biochemistry and Pharmacy, Universidad Nacional del Sur, Bahia blanca 8000, Buenos Aires, Argentina.
Department of Biology, Biochemistry and Pharmacy, Universidad Nacional del Sur, and Neurobiology Department, Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB) Conicet, Bahía Blanca 8000, Buenos Aires, Argentina.
World J Stem Cells. 2021 Oct 26;13(10):1446-1479. doi: 10.4252/wjsc.v13.i10.1446.
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.
视网膜变性是全球视觉功能障碍的主要原因。尽管它包括多种眼部疾病，但视网膜色素上皮（RPE）细胞和光感受器细胞的丧失是其发病机制的主要因素。早期治疗包括多种疗法，如提供抗血管内皮生长因子以及许多存活和营养因子，在某些情况下，这些疗法可减缓变性的进展，但不能有效预防。眼部干细胞（SC）的发现促使人们提出了针对视网膜变性的细胞替代策略。使用不同类型SC的疗法，如视网膜祖细胞（RPC）、胚胎干细胞、多能干细胞（PSC）、诱导多能干细胞（iPSC）和间充质基质细胞，这些细胞能够自我更新并分化为多种细胞类型，已获得广泛支持。大量临床前研究评估了干细胞在动物模型中的移植，结果令人鼓舞。这项工作的目的是回顾不同的临床前和临床方法，分析所使用的干细胞类型、它们的疗效、安全性、细胞附着和整合情况、无肿瘤形成和免疫排斥反应，以确定哪些是最相关和成功的。此外，我们还研究了该领域仍未解决的问题和担忧。数据表明存在两种主要方法，旨在替代RPE细胞或光感受器。新出现的证据表明，RPC和iPSC是最佳候选者，不存在伦理问题且免疫排斥风险低。临床试验已经支持了干细胞治疗的安全性和有效性。仍有一些严重问题悬而未决，如肿瘤形成风险、移植细胞与宿主视网膜缺乏附着或整合、免疫排斥、细胞死亡，以及伦理问题。然而，该领域在过去几年取得的惊人进展使得在不久的将来设想出安全有效的治疗方法来恢复视力丧失成为可能。
