Table2_In vitro responses of human dermal fibroblasts to mechanical strain: A systematic review and meta-analysis.DOCX

In vitro research in the field of mechanotransducive regulation of dermal fibroblasts is characterized by highly variable methodology and contradictory results. The primary objective of this systematic review was to establish how in vitro mechanical stretch affects human dermal fibroblast function, by means of a quantitative synthesis of all available evidence. The secondary objectives were to examine the effects of covariates related to donor age, fibroblast origin, experimental treatments, and mechanical stimulation parameters on dermal fibroblast responsiveness to mechanical strain. Summary outcomes for fibroblast proliferation and collagen production were combined using a fixed-effects meta-analytical model. Subgroup analysis and meta-regression were used to investigate the effects of different conditions on the summary outcomes. Mechanical strain was found to not affect fibroblast proliferation in neonatal fibroblasts, while adult fibroblasts proliferation was significantly increased. Collagen production was significantly increased in response to mechanical stimulation, with Vitamin C stimulation as the most important covariate. Stretching frequency emerged as positively associated with fibroblast proliferation and negatively associated with collagen production. We conclude from this study that distinct differences exist in the effects of mechanical stretching between dermal fibroblasts from neonatal and adult donors, which will help to further elucidate the pathophysiological mechanism behind tension-induced scarring.

针对皮肤成纤维细胞（dermal fibroblasts）机械转导调控领域的体外研究，普遍存在实验方法学差异显著、研究结果相互矛盾的问题。本项系统综述（systematic review）的首要目标，是通过对所有现有证据进行定量整合（quantitative synthesis），明确体外机械拉伸如何影响人皮肤成纤维细胞的功能。其次要目标为探究供体年龄、成纤维细胞来源、实验处理方案及机械刺激参数等相关协变量，对皮肤成纤维细胞机械应变响应性的影响。本研究采用固定效应荟萃分析模型（fixed-effects meta-analytical model），对成纤维细胞增殖与胶原蛋白生成（collagen production）的汇总结局进行合并分析。通过亚组分析（subgroup analysis）与荟萃回归（meta-regression），探究不同实验条件对汇总结局的影响。研究结果显示，机械应变对新生儿成纤维细胞（neonatal fibroblasts）的增殖无显著影响，但可显著提升成人成纤维细胞（adult fibroblasts）的增殖水平。机械刺激可显著上调胶原蛋白生成水平，其中维生素C（Vitamin C）刺激是影响该结局的最重要协变量。拉伸频率与成纤维细胞增殖呈正相关，而与胶原蛋白生成呈负相关。本研究得出结论：新生儿与成人供体来源的皮肤成纤维细胞，其机械拉伸效应存在显著差异；该结果有助于进一步阐明张力诱导瘢痕形成（tension-induced scarring）背后的病理生理机制（pathophysiological mechanism）。