Ashland Specialties France, Sophia Antipolis, France.
J Cosmet Dermatol. 2023 Jul;22(7):2090-2098. doi: 10.1111/jocd.15675. Epub 2023 Feb 27.
The skin is a sensory organ, densely innervated with various types of sensory nerve endings, capable of discriminating touch, environmental sensations, proprioception, and physical affection. Neurons communication with skin cells confer to the tissue the ability to undergo adaptive modifications during response to environmental changes or wound healing after injury. Thought for a long time to be dedicated to the central nervous system, the glutamatergic neuromodulation is increasingly described in peripheral tissues. Glutamate receptors and transporters have been identified in the skin. There is a strong interest in understanding the communication between keratinocytes and neurons, as the close contacts with intra-epidermal nerve fibers is a favorable site for efficient communication. To date, various coculture models have been described. However, these models were based on non-human or immortalized cell line. Even the use of induced pluripotent stem cells (iPSCs) is posing limitations because of epigenetic variations during the reprogramming process.
In this study, we performed small molecule-driven direct conversion of human skin primary fibroblasts into induced neurons (iNeurons).
The resulting iNeurons were mature, showed pan-neuronal markers, and exhibited a glutamatergic subtype and C-type fibers characteristics. Autologous coculture of iNeurons with human primary keratinocytes, fibroblasts, and melanocytes was performed and remained healthy for many days, making possible to study the establishment of intercellular interactions.
Here, we report that iNeurons and primary skin cells established contacts, with neurite ensheathment by keratinocytes, and demonstrated that iNeurons cocultured with primary skin cells provide a reliable model to examine intercellular communication.
皮肤是一种感觉器官，密布着各种类型的感觉神经末梢，能够区分触觉、环境感觉、本体感觉和身体感觉。神经元与皮肤细胞的通讯使组织能够在对外界变化做出反应或受伤后愈合时进行适应性改变。谷氨酸能神经调制作用长期以来被认为是专门用于中枢神经系统的，但现在越来越多地在周围组织中被描述。在皮肤中已经鉴定出谷氨酸受体和转运体。人们强烈希望了解角质形成细胞和神经元之间的通讯，因为与表皮内神经纤维的紧密接触是进行有效通讯的有利部位。迄今为止，已经描述了各种共培养模型。然而，这些模型是基于非人类或永生化细胞系的。即使使用诱导多能干细胞（iPSCs）也存在局限性，因为在重编程过程中会发生表观遗传变化。
在这项研究中，我们使用小分子驱动的方法将人皮肤原代成纤维细胞直接转化为诱导神经元（iNeurons）。
得到的 iNeurons 成熟，表现出泛神经元标志物，并表现出谷氨酸能亚型和 C 型纤维的特征。进行了 iNeurons 与原代人角质形成细胞、成纤维细胞和黑素细胞的自体共培养，共培养物保持健康多日，使得研究细胞间相互作用的建立成为可能。
在这里，我们报告 iNeurons 和原代皮肤细胞建立了联系，角质形成细胞包绕轴突，并且证明与原代皮肤细胞共培养的 iNeurons 提供了一个可靠的模型来研究细胞间通讯。
