Institut National de la Santé et de la Recherche Médicale (Inserm) UMRS976, Université de Paris, Hôpital Saint-Louis, 75010 Paris, France.
Department of Dermatology, AP-HP, Hôpital Saint-Louis, 75010 Paris, France.
Int J Mol Sci. 2021 Mar 19;22(6):3130. doi: 10.3390/ijms22063130.
Endosome-derived small extracellular vesicles (EVs), often referred to as exosomes, are produced by almost all, if not all, cell types, and are critical for intercellular communication. They are composed of a lipid bilayer associated with membrane proteins and contain a payload of lipids, proteins and regulatory RNAs that depends on the parental cell physiological condition. By transferring their "cargo", exosomes can modulate the phenotype of neighboring and distant cells. Stem cells (SC) were widely studied for therapeutic applications regarding their regenerative/reparative potential as well as their immunomodulatory properties. Whether from autologous or allogeneic source, SC beneficial effects in terms of repair and regeneration are largely attributed to their paracrine signaling notably through secreted EVs. Subsequently, SC-derived EVs have been investigated for the treatment of various diseases, including inflammatory skin disorders, and are today fast-track cell-free tools for regenerative/reparative strategies. Yet, their clinical application is still facing considerable challenges, including production and isolation procedures, and optimal cell source. Within the emerging concept of "allogeneic-driven benefit" for SC-based therapies, the use of EVs from allogeneic sources becomes the pragmatic choice although a universal allogeneic cell source is still needed. As a unique temporary organ that ensures the mutual coexistence of two allogeneic organisms, mother and fetus, the human placenta offers a persuasive allogeneic stem cell source for development of therapeutic EVs. Advancing cell-free therapeutics nurtures great hope and provides new perspectives for the development of safe and effective treatment in regenerative/reparative medicine and beyond. We will outline the current state of the art in regard of EVs, summarize their therapeutic potential in the context of skin inflammatory disorders, and discuss their translational advantages and hurdles.
内体衍生的小细胞外囊泡（EVs），通常称为外泌体，几乎所有（如果不是全部）细胞类型都会产生，对于细胞间通讯至关重要。它们由与膜蛋白相关的脂质双层组成，并且包含取决于亲代细胞生理状态的脂质、蛋白质和调节 RNA 的有效载荷。通过转移它们的“货物”，外泌体可以调节邻近和远距离细胞的表型。干细胞（SC）由于其再生/修复潜力以及免疫调节特性而被广泛研究用于治疗应用。无论来自自体还是同种异体来源，SC 在修复和再生方面的有益效果主要归因于其旁分泌信号，特别是通过分泌的 EVs。随后，已经研究了 SC 衍生的 EV 用于治疗各种疾病，包括炎症性皮肤疾病，并且今天它们是快速发展的无细胞工具，用于再生/修复策略。然而，它们的临床应用仍然面临着相当大的挑战，包括生产和分离程序以及最佳的细胞来源。在基于 SC 治疗的“同种异体驱动益处”的新兴概念中，尽管仍然需要通用的同种异体细胞来源，但使用来自同种异体来源的 EV 成为了实用的选择。作为确保两个同种异体生物体（母亲和胎儿）相互共存的独特临时器官，人胎盘为开发治疗性 EV 提供了有说服力的同种异体干细胞来源。推进无细胞治疗为再生/修复医学及其他领域的安全有效治疗方法的发展带来了巨大的希望并提供了新的视角。我们将概述 EVs 的当前现状，总结它们在皮肤炎症性疾病背景下的治疗潜力，并讨论它们的转化优势和障碍。
