Bracha Peter, Moore Nicholas A, Ciulla Thomas A
a Glick Eye Institute, Department of Ophthalmology , Indiana University School of Medicine , Indianapolis , IN , USA.
b Retina Service , Midwest Eye Institute , Indianapolis , IN , USA.
Expert Opin Biol Ther. 2017 Sep;17(9):1113-1126. doi: 10.1080/14712598.2017.1346079. Epub 2017 Jun 30.
In age-related macular degeneration (AMD), stem cells could possibly replace or regenerate disrupted pathologic retinal pigment epithelium (RPE), and produce supportive growth factors and cytokines such as brain-derived neurotrophic factor. Induced pluripotent stem cells (iPSCs)-derived RPE was first subretinally transplanted in a neovascular AMD patient in 2014. Areas covered: Induced PSCs are derived from the introduction of transcription factors to adult cells under specific cell culture conditions, followed by differentiation into RPE cells. Induced PSC-derived RPE cells exhibit ion transport, membrane potential, polarized VEGF secretion and gene expression that is similar to native RPE. Despite having similar in vitro function, morphology, immunostaining and microscopic analysis, it remains to be seen if iPSC-derived RPE can replicate the myriad of in vivo functions, including immunomodulatory effects, of native RPE cells. Historically, adjuvant RPE transplantation during CNV resections were technically difficult and complicated by immune rejection. Autologous iPSCs are hypothesized to reduce the risk of immune rejection, but their production is time-consuming and expensive. Alternatively, allogenic transplantation using human leukocyte antigen (HLA)-matched iPSCs, similar to HLA-matched organ transplantation, is currently being investigated. Expert opinion: Challenges to successful transplantation with iPSCs include surgical technique, a pathologic subretinal microenvironment, possible immune rejection, and complications of immunosuppression.
在年龄相关性黄斑变性（AMD）中，干细胞有可能替代或再生受损的病理性视网膜色素上皮（RPE），并产生支持性生长因子和细胞因子，如脑源性神经营养因子。2014年，诱导多能干细胞（iPSC）来源的RPE首次被视网膜下移植到一名新生血管性AMD患者体内。涵盖领域：诱导性PSC是在特定细胞培养条件下通过将转录因子导入成体细胞而获得的，随后分化为RPE细胞。诱导性PSC来源的RPE细胞表现出离子转运、膜电位、极化的VEGF分泌以及与天然RPE相似的基因表达。尽管具有相似的体外功能、形态、免疫染色和显微镜分析，但iPSC来源的RPE是否能够复制天然RPE细胞的众多体内功能，包括免疫调节作用，仍有待观察。从历史上看，在脉络膜新生血管（CNV）切除术中辅助进行RPE移植技术上较为困难，且存在免疫排斥问题。自体iPSC被认为可以降低免疫排斥的风险，但其制备耗时且昂贵。或者，目前正在研究使用与人类白细胞抗原（HLA）匹配的iPSC进行同种异体移植，这类似于HLA匹配的器官移植。专家观点：iPSC成功移植面临的挑战包括手术技术、病理性视网膜下微环境、可能的免疫排斥以及免疫抑制的并发症。
