Cariba Solsa, Srivastava Avika, Bronsema Kendra, Kouthouridis Sonya, Zhang Boyang, Payne Samantha L
Department of Biomedical Sciences, University of Guelph, Guelph N1G 2W1, Canada.
Department of Chemical Engineering, McMaster University, Hamilton L8S 4L8, Canada.
ACS Biomater Sci Eng. 2024 Dec 9;10(12):7566-7576. doi: 10.1021/acsbiomaterials.4c01482. Epub 2024 Nov 27.
Cutaneous wound healing is a complex process involving various cellular and molecular interactions, resulting in the formation of a collagen-rich scar with imperfect function and morphology. Dermal fibroblasts are crucial to successful wound healing, migrating to the wound site where they are activated to provide extracellular matrix remodeling and wound closure. Peripheral nerves have been shown to play an important role in wound healing, with loss or damage to these nerves often leading to impaired healing and the formation of chronic nonhealing wounds. Previous research has suggested that sensory nerves secrete trophic factors that can regulate wound healing, including fibroblast activation; however, the direct cell-cell interaction between nerves and fibroblasts has not been extensively studied. To address this knowledge gap, we developed an co-culture model using a device called the IFlowPlate. This model supports the long-term viability of multiple cell types while allowing for direct contact between sensory nerve cells and dermal fibroblasts. Using the IFlowPlate, we demonstrate that co-culture of dorsal root ganglia with dermal fibroblasts increases fibroblast proliferation, collagen and α-smooth muscle actin expression, and secretion of pro-wound healing factors, suggesting that nerves can promote wound healing by modulating fibroblast activation. The IFlowPlate offers a user-friendly and high-throughput platform to study the in vitro interactions between nerves and a variety of cell types that can be applied to wound healing and other important biological processes.
皮肤伤口愈合是一个复杂的过程，涉及多种细胞和分子相互作用，最终形成功能和形态均不完善的富含胶原蛋白的瘢痕。真皮成纤维细胞对伤口的成功愈合至关重要，它们迁移到伤口部位并被激活，以提供细胞外基质重塑和伤口闭合。外周神经在伤口愈合中发挥着重要作用，这些神经的损伤或缺失通常会导致愈合受损和慢性不愈合伤口的形成。先前的研究表明，感觉神经分泌的营养因子可以调节伤口愈合，包括成纤维细胞的激活；然而，神经与成纤维细胞之间直接的细胞间相互作用尚未得到广泛研究。为了填补这一知识空白，我们使用一种名为IFlowPlate的装置开发了一种共培养模型。该模型支持多种细胞类型的长期存活，同时允许感觉神经细胞与真皮成纤维细胞直接接触。使用IFlowPlate，我们证明背根神经节与真皮成纤维细胞共培养可增加成纤维细胞增殖、胶原蛋白和α-平滑肌肌动蛋白表达以及促伤口愈合因子的分泌，这表明神经可以通过调节成纤维细胞的激活来促进伤口愈合。IFlowPlate提供了一个用户友好且高通量的平台，用于研究神经与多种细胞类型之间的体外相互作用，可应用于伤口愈合和其他重要的生物学过程。
