Moreno Sarah E, Massee Michelle, Koob Thomas J
MiMedx Group, Inc, Marietta, Georgia, USA.
JID Innov. 2021 May 6;1(2):100020. doi: 10.1016/j.xjidi.2021.100020. eCollection 2021 Jun.
Excessive fibrosis affects more than 100 million patients yearly, leading to the accumulation of extracellular matrix that compromises tissue architecture and impedes its function. Intrinsic properties of the amniotic membrane have alluded to its potential to inhibit excessive fibrosis; therefore, this study aimed to investigate the effects of dehydrated human amnion/chorion membrane (dHACM) on dermal fibroblasts and their role in fibrotic pathways. Human dermal fibroblasts were stimulated with TGFβ1, triggering myofibroblast-like characteristics in vitro. Subsequent addition of dHACM in the continued presence of TGFβ1 inhibited downstream signaling, leading to a reduction in the expression of known fibrotic and extracellular matrix genes. In addition, dHACM decreased alpha-smooth muscle actin, a stress filament responsible for contractile activity in scarring. The functional outcome of these effects was observed in an ex vivo model for cellular contraction. Hyperactivation of TGFβ signaling increased the contractile capacity of myofibroblasts embedded within a collagen substrate. Simultaneous addition of dHACM treatment prevented the marked contraction, which is likely a direct result of the inhibition of TGFβ signaling mentioned earlier. These observations may support the use of dHACM in the regulation of fibroblast activity as it relates to tissue fibrosis.
每年有超过1亿患者受到过度纤维化的影响，导致细胞外基质积累，破坏组织结构并阻碍其功能。羊膜的内在特性暗示了其抑制过度纤维化的潜力；因此，本研究旨在探讨脱水人羊膜/绒毛膜（dHACM）对真皮成纤维细胞的影响及其在纤维化途径中的作用。用TGFβ1刺激人真皮成纤维细胞，在体外诱导出成肌纤维细胞样特征。在持续存在TGFβ1的情况下随后添加dHACM可抑制下游信号传导，导致已知纤维化和细胞外基质基因的表达减少。此外，dHACM降低了α-平滑肌肌动蛋白，这是一种负责瘢痕收缩活动的应力丝。在细胞收缩的体外模型中观察到了这些作用的功能结果。TGFβ信号的过度激活增加了嵌入胶原基质中的成肌纤维细胞的收缩能力。同时添加dHACM处理可防止明显的收缩，这可能是前面提到的TGFβ信号抑制的直接结果。这些观察结果可能支持将dHACM用于调节与组织纤维化相关的成纤维细胞活性。
