Cellular uptake pathways for mesenchymal stem cell-derived exosomes (MSC-Exo uptake pathways)

Mesenchymal stem cell-derived exosomes (MSC-Exos) are nano-sized extracellular vesicles that facilitate intercellular communication by delivering functional cargo, including proteins, lipids, and various RNA species, to recipient cells (Mulcahy et al., 2014). The cellular uptake of these exosomes is not mediated by a single receptor but occurs through multiple, often redundant, pathways involving non-specific cellular components such as the actin cytoskeleton, dynamin, and lipid rafts (Costa et al., 2018). Primary mechanisms include clathrin-mediated endocytosis, caveolae-dependent endocytosis, macropinocytosis, phagocytosis, and direct fusion with the plasma membrane (Gurung et al., 2021). These pathways are essential for the therapeutic effects of MSCs in regenerative medicine, as they enable the internalization of pro-regenerative and anti-inflammatory signals. However, because these pathways rely on fundamental cellular machinery, targeting them specifically for therapeutic modulation remains a challenge due to potential systemic toxicity and lack of cell-type specificity. Research in this area focuses on identifying the predominant uptake route in specific disease contexts to optimize the delivery and efficacy of exosome-based therapeutics (Mulcahy et al., 2014).

Other names

MSC-derived extracellular vesicle uptakeMSC-Exo internalization mechanismsEndocytic pathways for MSC exosomesMSC-EV internalization

Inhibition of dynamin-dependent endocytosis, disruption of clathrin-coated pit formation, inhibition of actin polymerization, or blockage of Na+/H+ exchange to prevent macropinocytosis.