Needle-Free Injection of Exosomes Derived from Human Dermal Fibroblast Spheroids Ameliorates Skin Photoaging
Needle-Free Injection of Exosomes Derived from Human Dermal Fibroblast Spheroids Ameliorates Skin Photoaging
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DOI：
10.1021/acsnano.9b04384
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发表时间：
2019-10-01
期刊：
影响因子：
17.1
通讯作者：
Cheng, Ke
中科院分区：
文献类型：
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作者：
Hu, Shiqi;Li, Zhenhua;Cheng, Ke
人真皮成纤维细胞（HDFs）是真皮的主要细胞群，随着年龄的增长，其产生胶原和更新细胞间基质的能力逐渐丧失。一种已被美国食品和药物管理局批准的自体经皮注射HDF的临床应用旨在改善面部轮廓并减缓皮肤衰老。然而，所使用的自体HDF的质量根据患者的状态而变化，并且由于它们在扩增期间经历了许多传代。在这项研究中，因子和exosomes来自三维球体（3D HDF-XOs）和HDFs的单层培养（2D HDF-XOs）收集和比较。与2D HDF-XO相比，3D HDF-XO表达显著更高水平的金属蛋白酶组织抑制剂-1（TIMP-1）和差异表达的miRNA货物。接下来，在体外和裸鼠光老化模型中证明了3D HDF-XO在诱导胶原蛋白合成和抗衰老方面的功效。使用无针注射器来施用外来体处理。3D HDF-XO导致I型前胶原表达增加和MMP-1表达显著降低，主要通过下调肿瘤坏死因子-α（TNF-α）和上调转化生长因子β（TGF-β）。此外，3D-HDF-XOs组的真皮胶原沉积水平高于骨髓间充质干细胞来源的外泌体。这些结果表明，来自3D培养的HDF球状体的外泌体具有抗皮肤老化特性，并具有预防和治疗皮肤老化的潜力。
Human dermal fibroblasts (HDFs), the main cell population of the dermis, gradually lose their ability to produce collagen and renew intercellular matrix with aging. One clinical application for the autologous trans-dermis injection of HDFs that has been approved by the Food and Drug Administration aims to refine facial contours and slow down skin aging. However, the autologous HDFs used vary in quality according to the state of patients and due to many passages they undergo during expansion. In this study, factors and exosomes derived from three-dimensional spheroids (3D HDF-XOs) and the monolayer culture of HDFs (2D HDF-XOs) were collected and compared. 3D HDF-XOs expressed a significantly higher level of tissue inhibitor of metalloproteinases-1 (TIMP-1) and differentially expressed miRNA cargos compared with 2D HDF-XOs. Next, the efficacy of 3D HDF-XOs in inducing collagen synthesis and antiaging was demonstrated in vitro and in a nude mouse photoaging model. A needle-free injector was used to administer exosome treatments. 3D HDF-XOs caused increased procollagen type I expression and a significant decrease in MMP-1 expression, mainly through the downregulation of tumor necrosis factor-alpha (TNF-alpha) and the upregulation of transforming growth factor beta (TGF-beta). In addition, the 3D-HDF-XOs group showed a higher level of dermal collagen deposition than bone marrow mesenchymal stem cell-derived exosomes. These results indicate that exosomes from 3D cultured HDF spheroids have anti-skin-aging properties and the potential to prevent and treat cutaneous aging.