Extracellular vesicles derived from human gingival mesenchymal stem cells: a transcriptomic analysis

The human Gingival Mesenchymal Stem Cells (hGMSCs) have outstanding characteristics of proliferation and are able to differentiate into osteogenic, chondrogenic, adipogenic and neurogenic cell lineages. The extracellular vesicles (EVs) secreted by hGMSCs contain proteins, lipids, mRNA and microRNA that have emerged as important mediators of cell-to-cell communication. In this study, we analysed the transcriptome of hGMSCs-derived EVs using Next Generation Sequencing (NGS). The functional evaluation of the transcriptome highlighted 26 structural protein classes and the presence of "Non-coding RNAs". Our results showed that EVs contain several growth factors such as Transforming Growth Factor-beta (TGF-b), Fibroblast Growth Factor (FGF) and Vascular Endothelial Growth Factors (VEGF) implicated in osteoblast differentiation and in angiogenetic process. Furthermore, the transcriptomic analysis showed the presence of Glial cell-Derived Neurotrophic Factor (GDNF) family ligands and Neurotrophins involved in neuronal development. The NGS analysis also identified the presence of several interleukins among which some with anti-inflammatory action. Moreover, the transcriptome profile of EVs contained members of the Wnt family, involved in several biological processes, such as cellular proliferation and tissue regeneration. In conclusion, the huge amount of growth factors included in the hGMSCs-derived EVs could make them a big resource in regenerative medicine.

人牙龈间充质干细胞（human Gingival Mesenchymal Stem Cells，hGMSCs）具备优异的增殖特性，可定向分化为成骨、成软骨、成脂及神经源性细胞谱系。hGMSCs分泌的细胞外囊泡（extracellular vesicles，EVs）含有蛋白质、脂质、mRNA及微小RNA（microRNA），现已成为细胞间通讯的重要介导因子。本研究采用下一代测序技术（Next Generation Sequencing，NGS）对hGMSCs来源的EVs转录组进行了分析。对该转录组的功能注释结果显示，其包含26类结构蛋白，且存在“非编码RNA（Non-coding RNAs）”。研究结果表明，EVs中含有多种生长因子，如转化生长因子-β（Transforming Growth Factor-beta，TGF-β）、成纤维细胞生长因子（Fibroblast Growth Factor，FGF）及血管内皮生长因子（Vascular Endothelial Growth Factors，VEGF），这些因子均参与成骨细胞分化及血管生成过程。此外，转录组分析还发现EVs中存在胶质细胞源性神经营养因子（Glial cell-Derived Neurotrophic Factor，GDNF）家族配体与神经营养因子，二者均参与神经元发育过程。本次NGS分析还鉴定出多种白细胞介素，其中部分具有抗炎活性。此外，EVs的转录组谱中还包含Wnt家族成员，该家族参与细胞增殖、组织再生等多种生物学过程。综上，hGMSCs来源的EVs中蕴含丰富的生长因子，使其成为再生医学领域的重要资源库。