Environmental pH stress influences cellular secretion and uptake of extracellular vesicles

Abstract

Exosomes (extracellular vesicles/EVs) participate in cell–cell communication and contain bioactive molecules, such as microRNAs. However, the detailed characteristics of secreted EVs produced by cells grown under low pH conditions are still unknown. Here, we report that low pH in the cell culture medium significantly affected the secretion of EVs with increased protein content and zeta potential. The intracellular expression level and location of stably expressed GFP‐fused CD63 (an EV tetraspanin) in HeLa cells were also significantly affected by environmental pH. In addition, increased cellular uptake of EVs was observed. Moreover, the uptake rate was influenced by the presence of serum in the cell culture medium. Our findings contribute to our understanding of the effect of environmental conditions on EV‐based cell–cell communication.

Extracellular vesicles from oviductal and uterine fluids supplementation in sequential in vitro culture improves bovine embryo quality

“…Thus, some EVs still in dFCS could lead to a different effect than that of medium with BSA. Also, if culture medium supplementation can somehow affect uptake of EVs as in certain cell lines [ 68 ], this would affect cargo delivery and the response of target cell.…”

Extracellular vesicles and particles impact the systemic landscape of cancer

“…Mechanistically, induction of HIF‐1α supports enhanced EVP release during hypoxia in breast cancer cells (King et al , 2012), while hypoxia appears to enhance MVB biogenesis and release of endosome‐derived exosomes in prostate cancer (Panigrahi et al , 2018) and ovarian cancer (Dorayappan et al , 2018). Additionally, alterations in pH associated with decreased extracellular and increased intracellular pH are prevalent in cancer cells (White et al , 2017), and augmented exosome biogenesis associated with changes in MVB biogenesis and transport has been observed when cancer cells are cultured in more acidic medium (Boussadia et al , 2018; Nakase et al , 2021). Impairment of lysosomal function can also promote exosome release and alter exosomal cargo by breast cancer cells (Latifkar et al , 2019).…”

Natural Killer Cell-Derived Extracellular Vesicles as a Promising Immunotherapeutic Strategy for Cancer: A Systematic Review

“…The existence of physical and chemical barriers in TEM paired with the inhibitory factors from TD-EVs render the NK cells and other immune cells almost entirely incompetent. Cellular release and uptake of EVs are known to increase in acidic environments [ 88 ]. Additionally, the pH-related stress also increases the EVs’ protein content and surface electrokinetic potential (zeta potential) [ 89 ].…”