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A Molecular Analysis of Cytokine Content across Extracellular Vesicles,Secretions, and Intracellular Space from Different Site-Specific Adipose-Derived Stem Cells
Authors:Jerran Santos  Penelope V Dalla  Bruce K Milthorpe
Affiliation:Advanced Tissue Engineering and Stem Cell Biology Group, School of Life Sciences, University of Technology Sydney, Broadway, P.O. Box 123, Sydney 2007, Australia; (P.V.D.); (B.K.M.)
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.
Keywords:adipose-derived stem cells  extracellular vesicles  secretions  cytokines  multiplex assay  interaction networks
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