Mesenchymal stem cell (MSC)-based therapies have yielded beneficial effects in a broad range of preclinical models and clinical trials for human diseases. In the context of MSC transplantation, it is widely recognized that the main mechanism for the regenerative potential of MSCs is not their differentiation, with data revealing transient and low engraftment rates. Instead, MSCs therapeutic effects are mainly attributed to its secretome, i.e., paracrine factors secreted by these cells, further offering a more attractive and innovative approach due to the effectiveness and safety of a cell-free product. In this review, we will discuss the potential benefits of MSC-derived secretome in regenerative medicine with particular focus on respiratory, hepatic, and neurological diseases. Both free and vesicular factors of MSC secretome will be detailed. We will also address novel potential strategies capable of improving their healing potential, namely by delivering important regenerative molecules according to specific diseases and tissue needs, as well as non-clinical and clinical studies that allow us to dissect their mechanisms of action. MSC-derived secretome includes both soluble and non-soluble factors, organized in extracellular vesicles (EVs). Importantly, besides depending on the cell origin, the characteristics and therapeutic potential of MSC secretome is deeply influenced by external stimuli, highlighting the possibility of optimizing their characteristics through preconditioning approaches. Nevertheless, the clarity around their mechanisms of action remains ambiguous, whereas the need for standardized procedures for the successful translation of those products to the clinics urges.

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用于再生医学的间充质干细胞分泌组：我们处于什么位置？


基于间充质干细胞（MSC）的疗法在人类疾病的广泛临床前模型和临床试验中产生了有益的效果。在间充质干细胞移植的背景下，人们普遍认为间充质干细胞再生潜力的主要机制不是它们的分化，数据显示短暂且低的植入率。相反，间充质干细胞的治疗效果主要归因于其分泌组，即这些细胞分泌的旁分泌因子，由于无细胞产品的有效性和安全性，进一步提供了更具吸引力和创新性的方法。在这篇综述中，我们将讨论 MSC 衍生的分泌蛋白组在再生医学中的潜在益处，特别关注呼吸系统、肝脏和神经系统疾病。将详细介绍 MSC 分泌组的游离因子和囊泡因子。我们还将提出能够提高其治愈潜力的新的潜在策略，即根据特定疾病和组织需求提供重要的再生分子，以及使我们能够剖析其作用机制的非临床和临床研究。 MSC 衍生的分泌蛋白组包括可溶性和非可溶性因子，组织在细胞外囊泡 (EV) 中。重要的是，除了取决于细胞来源外，MSC分泌组的特性和治疗潜力还深受外部刺激的影响，这凸显了通过预处理方法优化其特性的可能性。然而，其作用机制的清晰度仍然不明确，而迫切需要标准化程序才能将这些产品成功转化为临床。