Santos Jerran, Dalla Penelope V, Milthorpe Bruce K
Advanced Tissue Engineering and Stem Cell Biology Group, School of Life Sciences, University of Technology Sydney, Sydney 2007, Australia.
Life (Basel). 2022 Mar 8;12(3):392. doi: 10.3390/life12030392.
Mesenchymal stem cells are a continually expanding area in research and clinical applications. Their usefulness and capacity to differentiate into various cells, particularly neural types, has driven the research area for several years. Neural differentiation has considerable usefulness. There are several successful differentiation techniques of mesenchymal stem cells that employ the use of small molecules, growth factors and commercially available kits and supplements. Phenotyping, molecular biology, genomics and proteomics investigation revealed a wealth of data about these cells during neurogenic differentiation. However, there remain large gaps in the knowledge base, particularly related to cytokines and how their role, drive mechanisms and the downstream signalling processes change with their varied expression throughout the differentiation process. In this study, adult mesenchymal stem cells were induced with neurogenic differentiation media, the cellular changes monitored by live-cell microscopy and the changes in cytokine expression in the intracellular region, secretion into the media and in the extracellular vesicle cargo were examined and analysed bioinformatically. Through this analysis, the up-regulation of key cytokines was revealed, and several neuroprotective and neurotrophic roles were displayed. Statistically significant molecules IFN-G, IL1B, IL6, TNF-A, have roles in astrocyte development. Furthermore, the cytokine bioinformatics suggests the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway is upregulated, supporting differentiation toward an astroglial lineage.
间充质干细胞是研究和临床应用中一个不断扩展的领域。它们的有用性以及分化为各种细胞，特别是神经细胞类型的能力，推动了该研究领域多年的发展。神经分化具有相当大的用途。有几种成功的间充质干细胞分化技术，它们使用小分子、生长因子以及市售的试剂盒和补充剂。表型分析、分子生物学、基因组学和蛋白质组学研究揭示了神经源性分化过程中关于这些细胞的大量数据。然而，知识库中仍存在很大差距，特别是与细胞因子以及它们在整个分化过程中如何随着表达变化而改变其作用、驱动机制和下游信号传导过程有关。在本研究中，用神经源性分化培养基诱导成人间充质干细胞，通过活细胞显微镜监测细胞变化，并对细胞内区域、分泌到培养基中以及细胞外囊泡货物中的细胞因子表达变化进行生物信息学检查和分析。通过该分析，揭示了关键细胞因子的上调，并显示出几种神经保护和神经营养作用。具有统计学意义的分子IFN-G、IL1B、IL6、TNF-A在星形胶质细胞发育中起作用。此外，细胞因子生物信息学表明Janus激酶/信号转导子和转录激活子（JAK/STAT）途径上调，支持向星形胶质细胞谱系的分化。
