Epithelial Therapeutics Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, North Bethesda, Maryland, United States of America.
Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, United States of America.
PLoS One. 2021 Jun 18;16(6):e0253669. doi: 10.1371/journal.pone.0253669. eCollection 2021.
The scratch assay is an in vitro technique used to analyze cell migration, proliferation, and cell-to-cell interaction. In the assay, cells are grown to confluence and then 'scratched' with a sterile instrument. For the cells in the leading edge, the resulting polarity induces migration and proliferation in attempt to 'heal' the modeled wound. Keloid scars are known to have an accelerated wound closure phenotype in the scratch assay, representing an overactivation of wound healing. We performed a qualitative review of the recent literature searching for inhibitors of scratch assay activity that were already available in topical formulations under the hypothesis that such compounds may offer therapeutic potential in keloid treatment. Although several shortcomings in the scratch assay literature were identified, caffeine and allicin successfully inhibited the scratch assay closure and inflammatory abnormalities in the commercially available keloid fibroblast cell line. Caffeine and allicin also impacted ATP production in keloid cells, most notably with inhibition of non-mitochondrial oxygen consumption. The traditional Chinese medicine, shikonin, was also successful in inhibiting scratch closure but displayed less dramatic impacts on metabolism. Together, our results partially summarize the strengths and limitations of current scratch assay literature and suggest clinical assessment of the therapeutic potential for these identified compounds against keloid scars may be warranted.
划痕实验是一种用于分析细胞迁移、增殖和细胞间相互作用的体外技术。在该实验中,细胞生长至汇合状态,然后用无菌仪器“划痕”。对于前沿的细胞,由此产生的极性诱导迁移和增殖,试图“愈合”模拟的伤口。众所周知,瘢痕疙瘩在划痕实验中具有加速的伤口闭合表型,代表伤口愈合的过度激活。我们对最近的文献进行了定性综述,寻找已经以局部制剂形式存在的划痕实验活性抑制剂,假设这些化合物可能在瘢痕疙瘩治疗中有治疗潜力。尽管在划痕实验文献中发现了几个缺点,但咖啡因和大蒜素成功地抑制了商业上可获得的瘢痕疙瘩成纤维细胞系的划痕实验闭合和炎症异常。咖啡因和大蒜素还影响了瘢痕疙瘩细胞中的 ATP 产生,最显著的是抑制非线粒体耗氧量。中药紫草素也成功地抑制了划痕闭合,但对代谢的影响不太显著。总之,我们的结果部分总结了当前划痕实验文献的优缺点,并建议对这些已鉴定化合物针对瘢痕疙瘩的治疗潜力进行临床评估可能是合理的。