Abstract
Cytokines are multifunctional small proteins that have a vital influence on inflammatory states of tissues and play a role in signalling and cellular control mechanisms. Cytokine expression has primarily been viewed as a form of direct secretion of molecules through an active transportation; however, other forms of active transport such as extracellular vesicles are at play. This is particularly important in stem cells where signalling molecules are key to communication managing the levels of proliferation, migration, and differentiation into mature cells. This study investigated cytokines from intracellular content, direct cellular secretions, and extracellular vesicles from adult adipose-derived stem cells isolated from three distinct anatomical locations: abdomen, thigh, and chin. The cells were cultured investigated using live cell microscopy, cytokine assays, and bioinformatics analysis. The cytokines quantified and examined from each sample type showed a distinct difference between niche areas and sample types. The varying levels of TNF-alpha, IL-6 and IL-8 cytokines were shown to play a crucial role in signalling pathways such as MAPK, ERK1/2 and JAK-STAT in cells. On the other hand, the chemotactic cytokines IL-1rn, Eotaxin, IP-10 and MCP-1 showed the most prominent changes across extracellular vesicles with roles in noncanonical signalling. By examining the local and tangential roles of cytokines in stem cells, their roles in signalling and in regenerative mechanisms may be further understood.
Highlights
Cytokines are a sizeable group of pleotropic small proteins that are produced by a range of cells [1]
The secretion of cytokines from nonimmune cells has displayed functional roles in a variety of development stages, acting as trophic factors initiating the repair and regeneration of cells [4]. This is important in stem-cell research as their expression and secretion have been explored in various capacities in mesenchymal stem or stromal cells [5,6]. Their role in adipose-derived stem cells (ADSCs) is slowly being elucidated and has received increased attention in recent research to understand their role in basal expression and during the differentiation process, as well as their possible therapeutic potential [6,7]
A Student’s t-test (Figure 2) on average cell count between biological replicates of each isolation showed no statistical differences between abdominal ADSC and thigh ADSC numbers; a statistical significance in average cell count was identified when compared to the chin ADSC isolations
Summary
Cytokines are a sizeable group of pleotropic small proteins that are produced by a range of cells [1] They are generally well known for their role in the inflammatory response and control in the immune system [2]. The secretion of cytokines from nonimmune cells has displayed functional roles in a variety of development stages, acting as trophic factors initiating the repair and regeneration of cells [4]. This is important in stem-cell research as their expression and secretion have been explored in various capacities in mesenchymal stem or stromal cells [5,6]. Subtle variations in concentrations and combination changes can have profound effects in cells response to a stimulus, ranging from restoring the local site to a state of equilibrium or driving changes across entire populations of cells by guiding signalling and differentiation [8]
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