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miR-410的抑制作用促进脐带血源性间充质干细胞直接向视网膜色素上皮细胞分化。

Inhibition by miR-410 facilitates direct retinal pigment epithelium differentiation of umbilical cord blood-derived mesenchymal stem cells.

作者信息

Choi Soon Won, Kim Jae-Jun, Seo Min-Soo, Park Sang-Bum, Shin Tae-Hoon, Shin Ji-Hee, Seo Yoojin, Kim Hyung-Sik, Kang Kyung-Sun

机构信息

Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.

Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.

出版信息

J Vet Sci. 2017 Mar 30;18(1):59-65. doi: 10.4142/jvs.2017.18.1.59.

Abstract

Retinal pigment epithelium (RPE) is a major component of the eye. This highly specialized cell type facilitates maintenance of the visual system. Because RPE loss induces an irreversible visual impairment, RPE generation techniques have recently been investigated as a potential therapeutic approach to RPE degeneration. A microRNA-based technique is a new strategy for producing RPE cells from adult stem cell sources. Previously, we identified that antisense microRNA-410 (anti-miR-410) induces RPE differentiation from amniotic epithelial stem cells. In this study, we investigated RPE differentiation from umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) via anti-miR-410 treatment. We identified miR-410 as a RPE-relevant microRNA in UCB-MSCs from among 21 putative human RPE-depleted microRNAs. Inhibition of miR-410 induces overexpression of immature and mature RPE-specific factors, including MITF, LRAT, RPE65, Bestrophin, and EMMPRIN. The RPE-induced cells were able to phagocytize microbeads. Results of our microRNA-based strategy demonstrated proof-of-principle for RPE differentiation in UCB-MSCs by using anti-miR-410 treatment without the use of additional factors or exogenous transduction.

摘要

视网膜色素上皮(RPE)是眼睛的主要组成部分。这种高度特化的细胞类型有助于维持视觉系统。由于RPE的丧失会导致不可逆的视力损害,因此最近人们对RPE生成技术作为RPE变性的一种潜在治疗方法进行了研究。基于微小RNA的技术是一种从成体干细胞来源产生RPE细胞的新策略。此前,我们发现反义微小RNA-410(anti-miR-410)可诱导羊膜上皮干细胞向RPE分化。在本研究中,我们通过anti-miR-410处理研究了脐带血来源的间充质干细胞(UCB-MSCs)向RPE的分化。我们从21种假定的人类RPE缺失微小RNA中鉴定出miR-410是UCB-MSCs中与RPE相关的微小RNA。抑制miR-410可诱导未成熟和成熟RPE特异性因子的过表达,包括MITF、LRAT、RPE65、Bestrophin和EMMPRIN。诱导生成的RPE细胞能够吞噬微珠。我们基于微小RNA的策略的结果证明了通过使用anti-miR-410处理在UCB-MSCs中进行RPE分化的原理,无需使用其他因子或外源性转导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acd1/5366303/050c4f5c125a/jvs-18-59-g001.jpg

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