Human fibrocyte-derived exosomes accelerate wound healing in genetically diabetic mice
Human fibrocyte-derived exosomes accelerate wound healing in genetically diabetic mice
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DOI：
10.1016/j.bbrc.2015.09.166
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发表时间：
2015-11-13
影响因子：
3.1
通讯作者：
Nissen, Erwin
中科院分区：
文献类型：
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作者：
Geiger, Adolf;Walker, Audrey;Nissen, Erwin
糖尿病溃疡在全球范围内是一个巨大的社会和医疗负担，目前的治疗策略几乎没有反应。本研究旨在评估人循环纤维细胞分泌的外泌体的治疗潜力，所述纤维细胞是通过旁分泌信号传导参与正常伤口愈合的间充质祖细胞群体。在存在成纤维细胞生长因子2的情况下，从依次用血小板衍生生长因子-BB和转化生长因子-β 1刺激的细胞释放的外泌体未显示出潜在的免疫原性。这些外泌体表现出体外促血管生成特性，激活糖尿病皮肤成纤维细胞，诱导糖尿病角质形成细胞的迁移和增殖，并加速体内糖尿病小鼠的伤口闭合。外泌体货物的重要组分是热休克蛋白-90 α、总的和活化的信号转导子和转录激活子3、促血管生成（miR-126、miR-130 a、miR-132）和抗炎（miR-124 a、miR-125 b）microRNA以及调节胶原沉积的microRNA（miR-21）。这项概念验证研究证明了使用纤维细胞衍生的外泌体治疗糖尿病溃疡的可行性。(C)2015 Elsevier Inc. All rights reserved.
Diabetic ulcers represent a substantial societal and healthcare burden worldwide and scarcely respond to current treatment strategies. This study was addressed to evaluate the therapeutic potential of exosomes secreted by human circulating fibrocytes, a population of mesenchymal progenitors involved in normal wound healing via paracrine signaling. The exosomes released from cells sequentially stimulated with platelet-derived growth factor-BB and transforming growth factor-beta 1, in the presence of fibroblast growth factor 2, did not show potential immunogenicity. These exosomes exhibited in-vitro proangiogenic properties, activated diabetic dermal fibroblasts, induced the migration and proliferation of diabetic keratinocytes, and accelerated wound closure in diabetic mice in vivo. Important components of the exosomal cargo were heat shock protein-90 alpha, total and activated signal transducer and activator of transcription 3, proangiogenic (miR-126, miR-130a, miR-132) and anti-inflammatory (miR124a, miR-125b) microRNAs, and a microRNA regulating collagen deposition (miR-21). This proof-of-concept study demonstrates the feasibility of the use of fibrocytes-derived exosomes for the treatment of diabetic ulcers. (C) 2015 Elsevier Inc. All rights reserved.