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Extracellular Vesicles (EVs)
Published in Peixuan Guo, Kirill A. Afonin, RNA Nanotechnology and Therapeutics, 2022
Alice Braga, Giulia Manferrari, Jayden A. Smith, Stefano Pluchino
Intercellular signaling is a finely regulated process fundamental to sustaining homeostasis and proper functioning of multicellular organisms. Cell-to-cell communication occurs through a diversity of chemical messengers, including small molecules, proteins, glycoproteins, lipids, growth factors, and even nucleic acids. These signaling molecules can act on the source cell via autocrine signaling, or adjacent cells via juxtracrine signaling, targeting neighbors direct contact via the formation of cell junctions (e.g. gap junctions). Soluble messengers like hormones, cytokines, and chemokines can also be released to act over longer distances through paracrine and endocrine signaling. In recent times, relatively long-distance (> 100 μm) cell-to-cell connections via membrane nanotubes have been described as another putative means of intercellular signaling for the exchange of genetic information or transfer of pathogens between distal cells (Davis and Sowinski 2008). Interestingly, these nanotubules seem to impede small molecules trafficking, facilitating instead the transfer of vesicle-packaged material (Rustom et al. 2004). Signaling vesicle secretion has been described in a multitude of different cell types, yet only a few specialized cases of short-range cell-to-cell communication mediated by EVs (e.g. synaptic exchanges between neurons (Sudhof 2004)) were formally recognized as canonical.
Cell Adhesion in Animal Cell Culture: Physiological and Fluid-Mechanical Implications
Published in Martin A. Hjortso, Joseph W. Roos, Cell Adhesion, 2018
Manfred R. Koller, Eleftherios T. Papoutsakis
In some cases, both the adhesion of a cell and its consequent stimulation may be mediated by the same membrane-bound factor. Several growth and morphogenesis factors are known to be produced as membrane-anchored precursors. These include factors that have the consensus EGF-like structure, such as EGF itself, and transforming growth factor-α (TGF-α) (79). Once the TGF-α precursor becomes anchored to the membrane, the actual TGF-α portion is cleaved off to give the soluble growth factor. Apparently, however, this cleavage process is relatively inefficient, and the membrane-bound growth factor precursor may remain stable for several hours (80). This membrane-anchored growth factor is free to bind to its receptor during this time, which in effect will bind two cells together through a growth factor-receptor complex. The same interaction will also result in stimulation of the cell that is expressing the growth factor receptor. This dual interaction has been demonstrated for the interaction between the TGF-α precursor and the EGF receptor. The TGF-α was expressed in a bone marrow stromal cell line, which was then able to bind and stimulate proliferation of a hematopoietic progenitor cell line that does not bind to cells without the TGF-α (see Sec. 6 for a discussion of the hematopoietic system) (80). The term “juxtacrine” was coined to describe this type of intercellular stimulation mediated by the binding of a membrane-bound growth factor to its receptor on an adjacent cell. This interaction may facilitate cell-cell adhesion and also mediate cell homing to appropriate cells that allow their stimulation and proliferation. This type of cellular homing is important in bone marrow cultures and is discussed further in Sec. 6.
Influence of extracellular cues of hydrogel biomaterials on stem cell fate
Published in Journal of Biomaterials Science, Polymer Edition, 2022
Haley Barnett, Mariya Shevchuk, Nicholas A. Peppas, Mary Caldorera-Moore
In addition to physical cues, the natural ECM provides biochemical cues that modulate cell behavior. Matrix proteins such as fibronectin and laminin allow for cell binding to the surface [18], which provides spatial control that can promote cell-to-cell communication. Contact-dependent, cell-cell signaling (juxtacrine signaling) provides constant morphogenic cues, while the diffusion of soluble signals from neighboring cells (paracrine signaling) transiently affects proximal populations of cells. These interactions between cell populations influence a range of stem cell behaviors including the induction of differentiation [19] and self-renewal properties [20–23]. Positioning within the stem cell microenvironment, achieved by the spatial distribution of the ECM and cell-cell contacts, physically confines stem cell self-renewal and differentiation behavior by guiding the position of the mitotic axis in asymmetric division [24,25]. The ECM also consists of proteoglycans that sequester soluble signals that bind to cell receptors and direct cell migration, proliferation, and differentiation [26].