Extracellular vesicles derived from mesenchymal stem cells - a novel therapeutic tool in infectious diseases

Abstract

Extracellular vesicles (EVs) are nano-sized lipid-bilayer encapsulated vesicles produced by the cells. These EVs are released into the surrounding space by almost all cell types. The EVs help in intercellular communication via their payloads which contain various proteins, lipids, and nucleic acids generated from the donor cells and allow for synergistic responses in surrounding cells. In recent years, EVs have been increasingly important in treating infectious diseases, including respiratory tract infections, urinary tract infections, wound infections, sepsis, and intestinal infections. Studies have confirmed the therapeutic value of mesenchymal stem cell-derived EVs (MSC-EVs) for treating infectious diseases to eliminate the pathogen, modulate the resistance, and restore tissue damage in infectious diseases. This can be achieved by producing antimicrobial substances, inhibiting pathogen multiplication, and activating macrophage phagocytic activity. Pathogen compounds can be diffused by inserting them into EVs produced and secreted by host cells or by secreting them as microbial cells producing EVs carrying signalling molecules and DNA shielding infected pathogens from immune attack. EVs play a key role in infectious pathogenesis and hold great promise for developing innovative treatments. In this review, we discuss the role of MSC-EVs in treating various infectious diseases.

Keywords: Exosomes; Extracellular vesicles; Mesenchymal stem cells; Stem cell therapy; Wound infections.

Fig. 1

Biogenesis of extracellular vesicles. Exosomes are generated by budding of early endosomes into intraluminal vesicles (ILVs) that are released upon fusion of multivesicular bodies (MVBs) with plasma membrane. MVBs usually have one of two destinies either lysosomal degradation or their release on fusion with plasma membrane, allowing their contents to be released into the extracellular environment. This release can be either ESCRT dependent or ESCRT independent. Microvesicles are generated by outward budding of the plasma membrane into the extracellular region. Apoptotic bodies are formed by the blebbing of plasma membrane from apoptotic cells

Fig. 2

Potential therapeutic role of MSC-EVs in infectious diseases

Fig. 3

MSC-EVs can produce different kinds of miRNAs causing M2 macrophage polarisation that in turn results in increased cytokine IL-10, VEGF and TGF-β and decreased NF-κB and IL-8 expression. Furthermore, the EVs are internalised into endothelial cells, monocytes, neutrophils and macrophages. As a result of which there is less pro-inflammatory cytokine production, improved phagocytic activity and increased tissue regeneration

Fig. 4

MSC-EVs expressing ACE2 receptor competitively binds to SARS-CoV-2 and prevents the binding of SARS-CoV-2 to AT2 cells

Fig. 5

Wound healing is enhanced by the local application of scaffolds carrying MSC-EVs. These MSC-EVs enhance the effects of different cell types that are involved in wound healing. These cells include fibroblasts, keratinocytes, endothelial cells and immune cells

Fig. 6

MSC-EVs have the ability to deliver antioxidant enzymes like superoxide dismutase (SOD), glutathione S-transferase (GST) and catalase (CAT) directly into the target cells. These anti-oxidant enzymes effectively reduce oxidative stress and inflammation in intestines