Extracellular Vesicles from Mesenchymal Stromal Cells for the Treatment of Inflammation-Related Conditions

Abstract

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.

The Role of Extracellular Vesicles in the Pathogenesis, Diagnosis, and Treatment of Osteoarthritis

“…However, there are still certain clinical impacts of the direct transplantation of stem cells into target tissues such as tumorigenicity, immune incompatibility, and chromosomal aberrations [ 4 , 5 ]. Because the regeneration, anti-inflammatory, immune regulation, and other functions of stem cells are mainly through their paracrine function [ 6 ], extracellular vesicles (EVs) have been widely studied. As intercellular communication carriers, EVs transfer biologically active lipids, proteins, and nucleic acids including mRNA, microRNA, and long-chain non-coding RNA (lncRNA) between cells, thereby triggering biological responses in recipient cells.…”

Microfluidic Tools for Enhanced Characterization of Therapeutic Stem Cells and Prediction of Their Potential Antimicrobial Secretome

“…To sum up, there is growing evidence that, as part of the secretome, the extracellular vesicles (EVs) will be the next effective therapeutic agents deriving from MSCs. Current research concerning MSC-EVs [125,126] as anti-inflammatory [127] and pro-regenerative agents for treating inflammation-related conditions has shown therapeutic potential in preclinical studies as recently reviewed [128]. In most of the cases persistent infections led to increased tissue damage associated with excessive duration of inflammation.…”

“…There has been speculation about the role of EVs in mediating cell protection [138] and the host response to infection [128]. Recently, it was also reported that human EVs and exosomes act as cellular decoys and are produced by cells for protection against bacterial pathogens [139,140].…”

“…Generally, since EVs display low immunogenicity, are non-mutagenic [141], and have great physiochemical stability, they will be promising protagonists of future nanomedicine [141]. Considering the therapeutic effects exerted by MSCs, the development of an EV-based approach aspired to translate their anti-inflammatory agents into a future nanosized treatment for inflammation-related conditions [128].…”

Therapeutic Implications of Mesenchymal Stromal Cells and Their Extracellular Vesicles in Autoimmune Diseases: From Biology to Clinical Applications

“…Aside from the aforementioned bioactive molecules, extracellular vesicles are increasingly being recognized as crucial mediators of MSCs’ biological functions. This concept has been supported by the fact that ΜSC-derived EVs can mimic the biological properties of their parental cells [ 109 ] and can exert similar anti-inflammatory, antiapoptotic, proangiogenic, and immunomodulatory effects in various disease models [ 110 , 111 ]. In the next section, the biology of EVs will be discussed and the immunomodulatory role of MSC-EVs will be explored.…”