Parekh Aron, Hebda Patricia A
Department of Otolaryngology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Curr Pathobiol Rep. 2017 Sep;5(3):271-277. doi: 10.1007/s40139-017-0149-3. Epub 2017 Jul 28.
Injured skin in the mammalian fetus can heal regeneratively due to the ability of fetal fibroblasts to effectively reorganize the extracellular matrix (ECM). This process occurs without fetal fibroblasts differentiating into highly contractile myofibroblasts which cause scarring and fibrosis in adult wounds. Here, we provide a brief review of fetal wound healing and the evidence supporting a unique contractile phenotype in fetal fibroblasts. Furthermore, we discuss the biomechanical role of the ECM in driving myofibroblast differentiation in wound healing and the implications for new clinical modalities based on the biophysical properties of fetal fibroblasts.
We and others have found that fetal fibroblasts are refractory to the environmental stimuli necessary for myofibroblast differentiation in adult wound healing including mechanical stress.
Understanding the biomechanical mechanisms that regulate the contractile phenotype of fetal fibroblasts may unlock new avenues for anti-scarring therapies that target myofibroblast differentiation of adult fibroblasts.
哺乳动物胎儿受伤的皮肤能够再生愈合,这是因为胎儿成纤维细胞有能力有效重组细胞外基质(ECM)。此过程发生时,胎儿成纤维细胞不会分化为导致成人伤口瘢痕形成和纤维化的高收缩性肌成纤维细胞。在此,我们简要综述胎儿伤口愈合以及支持胎儿成纤维细胞独特收缩表型的证据。此外,我们讨论细胞外基质在伤口愈合中驱动肌成纤维细胞分化的生物力学作用,以及基于胎儿成纤维细胞生物物理特性的新临床模式的意义。
我们和其他人发现,胎儿成纤维细胞对成人伤口愈合中肌成纤维细胞分化所需的环境刺激(包括机械应力)具有抗性。
了解调节胎儿成纤维细胞收缩表型的生物力学机制可能为针对成人成纤维细胞肌成纤维细胞分化的抗瘢痕治疗开辟新途径。