Molecular Dynamics of Cytokine Interactions and Signalling of Mesenchymal Stem Cells Undergoing Directed Neural-like Differentiation

Abstract

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.

Neurogenic marker expression in differentiating human adipose derived adult mesenchymal stem cells

“…Cytokine changes are commonly seen following ADSC differentiation in a number of conditions ( 18 , 44 , 45 ). CNPase expression can also be influenced by the presence of different cytokines.…”

Interaction of Neural Stem Cells (NSCs) and Mesenchymal Stem Cells (MSCs) as a Promising Approach in Brain Study and Nerve Regeneration

“…Such differen-tiated MSCs were shown to be more effective in the treatment of experimental autoimmune encephalitis mouse model than nondifferentiated MSCs [97]. It was also reported that MSCs changed their secretory properties in the presence of neurogenic differentiation media and those upregulated cytokines are known to be essential for astrocytes development [98]. Except for the addition of components influencing neural differentiation to culture media, other strategies are also being looked for to increase neurogenic potential of MSCs.…”

Adipose-Derived Stem Cells Spontaneously Express Neural Markers When Grown in a PEG-Based 3D Matrix

“…Not only are they highly abundant in the human body, they are also relatively easily accessible through subcutaneous adipose tissue liposuction, minimizing potential collection complications from more invasive cell collection methods like bone marrow aspirates [18]. Additionally, significant progress has been made in differentiating ADSCs toward neural cells; however, the most common method of differentiation is with 2D chemical inductions, which are not always stable [19][20][21][22][23][24][25][26]. Ahmadi et al [27] compared the stability of ADSCs neural differentiation between a 2D chemical induction protocol and a sphere formation protocol.…”