Adipose mesenchymal stem cells-derived exosomes attenuate retina degeneration of streptozotocin-induced diabetes in rabbits.
Adipose mesenchymal stem cells-derived exosomes attenuate retina degeneration of streptozotocin-induced diabetes in rabbits.
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DOI：
10.1177/1849454418807827
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发表时间：
2018-01
影响因子：
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通讯作者：
Shamardan RM
中科院分区：
文献类型：
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作者：
Safwat A;Sabry D;Ragiae A;Amer E;Mahmoud RH;Shamardan RM
本研究旨在评价间充质干细胞（MSCs）来源的外泌体在实验诱导的糖尿病（DM）兔模型视网膜再生中的作用。外来体是细胞外囊泡，其含有许多来自其来源细胞的microRNA（micRNA）、mRNA和蛋白质。通过静脉（IV）注射链脲佐菌素在家兔中诱导DM。从兔的脂肪组织中分离MSC。通过超离心从MSC中提取外泌体。通过不同途径（IV、结膜下（SC）和眼内（IO））注射外来体。通过视网膜组织的组织病理学检查和通过实时聚合酶链反应评估视网膜组织中的micRNA-222表达水平来进行治疗评价。在组织学上，SC外泌体治疗后12周，视网膜的细胞组分被组织在明确的层中，而IO外泌体注射显示明确的视网膜层，其明显类似于正常视网膜的层。然而，在IV外泌体注射后，视网膜出现厚度增加的不规则神经节层。与健康对照和其他糖尿病组相比，糖尿病对照中的MicRNA-222表达水平显著降低（分别为0.06 ± 0.02对0.51 ± 0.07、0.28 ± 0.08、0.48 ± 0.06和0.42 ± 0.11）。我们检测到血清葡萄糖与视网膜组织micRNA-222表达水平之间存在显著负相关性（r =-0.749，p = 0.001）。我们可以将micRNA-222的表达增加与施用MSC衍生的外泌体后视网膜的再生变化相关联。该研究证明了兔脂肪组织来源的MSC外泌体在视网膜修复中的效力。因此，外泌体通过其在包括micRNA-222在内的许多因子的穿梭中的作用而被认为是基于MSC的治疗中的新型治疗载体。
This study aimed to evaluate the effect of mesenchymal stem cells (MSCs)–derived exosomes in retina regeneration of experimentally induced diabetes mellitus (DM) in a rabbit model. Exosomes are extracellular vesicles that contain many microRNAs (micRNAs), mRNAs, and proteins from their cells of origin. DM was induced by intravenous (IV) injection of streptozotocin in rabbits. MSCs were isolated from adipose tissue of rabbits. Exosomes were extracted from MSCs by ultracentrifugation. Exosomes were injected by different routes (IV, subconjunctival (SC), and intraocular (IO)). Evaluation of the treatment was carried out by histopathological examination of retinal tissues and assessment of micRNA-222 expression level in retinal tissue by real-time polymerase chain reaction. Histologically, by 12 weeks following SC exosomal treatment, the cellular components of the retina were organized in well-defined layers, while IO exosomal injection showed well-defined retinal layers which were obviously similar to layers of the normal retina. However, the retina appeared after IV exosomal injection as irregular ganglionic layer with increased thickness. MicRNA-222 expression level was significantly reduced in diabetic controls when compared to each of healthy controls and other diabetic groups with IV, SC, and IO routes of injected exosomes (0.06 ± 0.02 vs. 0.51 ± 0.07, 0.28 ± 0.08, 0.48 ± 0.06, and 0.42 ± 0.11, respectively). We detected a significant negative correlation between serum glucose and retinal tissue micRNA-222 expression level (r = −0.749, p = 0.001). We can associate the increased expression of micRNA-222 with regenerative changes of retina following administration of MSCs-derived exosomes. The study demonstrates the potency of rabbit adipose tissue–derived MSCs exosomes in retinal repair. So, exosomes are considered as novel therapeutic vectors in MSCs-based therapy through its role in shuttling of many factors including micRNA-222.