Nasir Nur Azida Mohd, Paus Ralf, Ansell David M
Centre for Dermatology Research, School of Biological Sciences, The University of Manchester, Manchester, United Kingdom.
School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia.
Wound Repair Regen. 2019 Jan;27(1):126-133. doi: 10.1111/wrr.12688. Epub 2018 Dec 21.
Ex vivo wounded human skin organ culture is an invaluable tool for translationally relevant preclinical wound healing research. However, studies incorporating this system are still underutilized within the field because of the low throughput of histological analysis required for downstream assessment. In this study, we use intravital fluorescent dye to lineage trace epidermal cells, demonstrating that wound re-epithelialization of human ex vivo wounds occurs consistent with an extending shield mechanism of collective migration. Moreover, we also report a relatively simple method to investigate global epithelial closure of explants in culture using daily fluorescent dye treatment and en face imaging. This study is the first to quantify healing of ex vivo wounds in a longitudinal manner, providing global assessments for re-epithelialization and tissue contraction. We show that this approach can identify alterations to healing with a known healing promoter. This methodological study highlights the utility of human ex vivo wounds in enhancing our understanding of mechanisms of human skin repair and in evaluating novel therapies to improve healing outcome.
体外创伤人皮肤器官培养是用于转化相关临床前伤口愈合研究的一种宝贵工具。然而，由于下游评估所需的组织学分析通量较低，该领域中纳入此系统的研究仍未得到充分利用。在本研究中，我们使用活体荧光染料对表皮细胞进行谱系追踪，证明人体外伤口的伤口再上皮化与集体迁移的扩展屏障机制一致。此外，我们还报告了一种相对简单的方法，即通过每日荧光染料处理和表面成像来研究培养物中外植体的整体上皮闭合。本研究首次以纵向方式量化体外伤口的愈合情况，提供了对再上皮化和组织收缩的整体评估。我们表明，这种方法可以识别已知愈合促进剂对愈合的影响。这项方法学研究突出了人体外伤口在增强我们对人类皮肤修复机制的理解以及评估改善愈合结果的新疗法方面的效用。
