Autologous micrograft accelerates endogenous wound healing response through ERK-induced cell migration
Autologous micrograft accelerates endogenous wound healing response through ERK-induced cell migration
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DOI：
10.1038/s41418-019-0433-3
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发表时间：
2020-05-01
影响因子：
12.4
通讯作者：
Sampaolesi, Maurilio
中科院分区：
文献类型：
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作者：
Balli, Martina;Vitali, Francesca;Sampaolesi, Maurilio
缺陷细胞迁移导致伤口愈合延迟（WH）和慢性皮肤损伤。自体微移植（AMG）疗法最近已成为一种新的有效和负担得起的治疗，能够提高伤口愈合能力。然而，AMG显示其有益作用的精确分子机制仍未揭示。在此，我们表明AMG通过加速成纤维细胞和角质形成细胞的迁移来改善皮肤再上皮化。更具体地，AMG处理的伤口显示出与成功伤口愈合相关的不可或缺的事件的改善，例如肉芽组织形成、组织化胶原蛋白含量和新形成的血管。我们证明，AMG富含一个池的WH相关的生长因子，可以提供一个更快的内源性伤口愈合反应的起始信号。这项工作将细胞迁移率的增加与细胞外信号调节激酶（ERK）信号通路的激活联系起来，随后是基质金属蛋白酶表达及其细胞外酶活性的增加。总的来说，我们揭示了AMG介导的伤口愈合转录特征，并阐明了AMG分子机制，支持其触发高度改善的伤口愈合过程的潜力。通过这种方式，我们提出了一个框架，为未来的AMG治疗皮肤组织再生应用的改进。
Defective cell migration causes delayed wound healing (WH) and chronic skin lesions. Autologous micrograft (AMG) therapies have recently emerged as a new effective and affordable treatment able to improve wound healing capacity. However, the precise molecular mechanism through which AMG exhibits its beneficial effects remains unrevealed. Herein we show that AMG improves skin re-epithelialization by accelerating the migration of fibroblasts and keratinocytes. More specifically, AMG-treated wounds showed improvement of indispensable events associated with successful wound healing such as granulation tissue formation, organized collagen content, and newly formed blood vessels. We demonstrate that AMG is enriched with a pool of WH-associated growth factors that may provide the starting signal for a faster endogenous wound healing response. This work links the increased cell migration rate to the activation of the extracellular signal-regulated kinase (ERK) signaling pathway, which is followed by an increase in matrix metalloproteinase expression and their extracellular enzymatic activity. Overall we reveal the AMG-mediated wound healing transcriptional signature and shed light on the AMG molecular mechanism supporting its potential to trigger a highly improved wound healing process. In this way, we present a framework for future improvements in AMG therapy for skin tissue regeneration applications.