Over the past two decades, mesenchymal stromal cells (MSCs) have demonstrated great potential in the treatment of inflammation-related conditions. Numerous early stage clinical trials have suggested that this treatment strategy has potential to lead to significant improvements in clinical outcomes. While promising, there remain substantial regulatory hurdles, safety concerns, and logistical issues that need to be addressed before cell-based treatments can have widespread clinical impact. These drawbacks, along with research aimed at elucidating the mechanisms by which MSCs exert their therapeutic effects, have inspired the development of extracellular vesicles (EVs) as anti-inflammatory therapeutic agents. The use of MSC-derived EVs for treating inflammation-related conditions has shown therapeutic potential in both in vitro and small animal studies. This review will explore the current research landscape pertaining to the use of MSC-derived EVs as anti-inflammatory and pro-regenerative agents in a range of inflammation-related conditions: osteoarthritis, rheumatoid arthritis, Alzheimer’s disease, cardiovascular disease, and preeclampsia. Along with this, the mechanisms by which MSC-derived EVs exert their beneficial effects on the damaged or degenerative tissues will be reviewed, giving insight into their therapeutic potential. Challenges and future perspectives on the use of MSC-derived EVs for the treatment of inflammation-related conditions will be discussed.
Obstructive sleep apnea (OSA) is a chronic disorder that involves a decrease or complete cessation of airflow during sleep. It occurs when the muscles supporting the soft tissues in the throat relax during sleep, causing narrowing or closure of the upper airway. Sleep apnea is a serious medical condition with an increased risk of cardiovascular complications and impaired quality of life. Continuous positive airway pressure (CPAP) is the most effective treatment for moderate to severe cases of OSA and is effective in mild sleep apnea. However, CPAP therapy is associated with the development of several nasal side effects and is inconvenient for the user, leading to low compliance rates. The effects of CPAP treatment on the upper respiratory system, as well as the pathogenesis of side effects, are incompletely understood and not adequately researched. To better understand the effects of CPAP treatment on the upper respiratory system, we developed an in vitro 3D-printed microfluidic platform. A nasal epithelial cell line, RPMI 2650, was then exposed to certain conditions to mimic the in vivo environment. To create these conditions, the microfluidic device was utilized to expose nasal epithelial cells grown and differentiated at the air–liquid interface. The airflow was similar to what is experienced with CPAP, with pressure ranging between 0 and 20 cm of H2O. Cells exposed to pressure showed decreased barrier integrity, change in cellular shape, and increased cell death (lactate dehydrogenase release into media) compared to unstressed cells. Stressed cells also showed increased secretions of inflammatory markers IL-6 and IL-8 and had increased production of ATP. Our results suggest that stress induced by airflow leads to structural, metabolic, and inflammatory changes in the nasal epithelium, which may be responsible for developing nasal side-effects following CPAP treatment.
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