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源自人羊膜上皮细胞的外泌体可加速伤口愈合并抑制瘢痕形成。

Exosomes derived from human amniotic epithelial cells accelerate wound healing and inhibit scar formation.

作者信息

Zhao Bin, Zhang Yijie, Han Shichao, Zhang Wei, Zhou Qin, Guan Hao, Liu Jiaqi, Shi Jihong, Su Linlin, Hu Dahai

机构信息

Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shannxi, China.

出版信息

J Mol Histol. 2017 Apr;48(2):121-132. doi: 10.1007/s10735-017-9711-x. Epub 2017 Feb 22.

Abstract

Wound healing is a highly orchestrated physiological process consisting of a complex events, and scarless wound healing is highly desired for the development and application in clinical medicine. Recently, we have demonstrated that human amniotic epithelial cells (hAECs) promoted wound healing and inhibited scar formation through a paracrine mechanism. However, exosomes (Exo) are one of the most important paracrine factors. Whether exosomes derived from human amniotic epithelial cells (hAECs-Exo) have positive effects on scarless wound healing have not been reported yet. In this study, we examined the role of hAECs-Exo on wound healing in a rat model. We found that hAECs, which exhibit characteristics of both embryonic and mesenchymal stem cells, have the potential to differentiate into all three germ layers. hAECs-Exo ranged from 50 to 150 nm in diameter, and positive for exosomal markers CD9, CD63, CD81, Alix, TSG101 and HLA-G. Internalization of hAECs-Exo promoted the migration and proliferation of fibroblasts. Moreover, the deposition of extracellular matrix (ECM) were partly abolished by the treatment of high concentration of hAECs-Exo (100 μg/mL), which may be through stimulating the expression of matrix metalloproteinase-1 (MMP-1). In vivo animal experiments showed that hAECs-Exo improved the skin wound healing with well-organized collagen fibers. Taken together, These findings represent that hAECs-Exo can be used as a novel hope in cell-free therapy for scarless wound healing.

摘要

伤口愈合是一个高度协调的生理过程,由一系列复杂事件组成,而无瘢痕伤口愈合在临床医学的发展和应用中备受期待。最近,我们已经证明人羊膜上皮细胞(hAECs)通过旁分泌机制促进伤口愈合并抑制瘢痕形成。然而,外泌体(Exo)是最重要的旁分泌因子之一。源自人羊膜上皮细胞的外泌体(hAECs-Exo)对无瘢痕伤口愈合是否具有积极作用尚未见报道。在本研究中,我们在大鼠模型中研究了hAECs-Exo对伤口愈合的作用。我们发现,具有胚胎干细胞和间充质干细胞特征的hAECs有分化为所有三个胚层的潜力。hAECs-Exo直径范围为50至150纳米,外泌体标志物CD9、CD63、CD81、Alix、TSG101和HLA-G呈阳性。hAECs-Exo的内化促进了成纤维细胞的迁移和增殖。此外,高浓度hAECs-Exo(100μg/mL)处理可部分消除细胞外基质(ECM)的沉积,这可能是通过刺激基质金属蛋白酶-1(MMP-1)的表达实现的。体内动物实验表明,hAECs-Exo改善了皮肤伤口愈合,胶原纤维排列整齐。综上所述,这些发现表明hAECs-Exo可作为无瘢痕伤口愈合的无细胞治疗新希望。

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