1 Department of Otolaryngology, University of California, Davis, Davis, California.
2 Drug Discovery Consortium, University of California, San Francisco, San Francisco, California.
Stem Cells Dev. 2019 Mar 15;28(6):398-409. doi: 10.1089/scd.2018.0200. Epub 2019 Feb 26.
Mesenchymal stem cells (MSCs) facilitate functional recovery in numerous animal models of inflammatory and ischemic tissue-related diseases with a growing body of research suggesting that exosomes mediate many of these therapeutic effects. It remains unclear, however, which types of proteins are packaged into exosomes compared with the cells from which they are derived. In this study, using comprehensive proteomic analysis, we demonstrated that human primed MSCs secrete exosomes (pMEX) that are packaged with markedly higher fractions of specific protein subclasses compared with their cells of origin, indicating regulation of their contents. Notably, we found that pMEX are also packaged with substantially elevated levels of extracellular-associated proteins. Fibronectin was the most abundant protein detected, and data established that fibronectin mediates the mitogenic properties of pMEX. In addition, treatment of SHSY5Y cells with pMEX induced the secretion of growth factors known to possess mitogenic and neurotrophic properties. Taken together, our comprehensive analysis indicates that pMEX are packaged with specific protein subtypes, which may provide a molecular basis for their distinct functional properties.
间充质干细胞（MSCs）在许多与炎症和缺血组织相关疾病的动物模型中促进功能恢复，越来越多的研究表明外泌体介导了许多这些治疗作用。然而，与它们来源的细胞相比，哪些类型的蛋白质被包装到外泌体中仍然不清楚。在这项研究中，我们使用全面的蛋白质组学分析表明，人类初始 MSCs 分泌的外泌体（pMEX）与它们的起源细胞相比，含有明显更高比例的特定蛋白质亚类，表明其内容物受到调节。值得注意的是，我们发现 pMEX 还被包裹在大量的细胞外相关蛋白中。纤连蛋白是检测到的最丰富的蛋白质，数据表明纤连蛋白介导 pMEX 的有丝分裂特性。此外，用 pMEX 处理 SHSY5Y 细胞诱导了具有有丝分裂和神经营养特性的生长因子的分泌。总之，我们的综合分析表明，pMEX 被特定的蛋白质亚型所包裹，这可能为它们独特的功能特性提供了分子基础。
