Application of exosomes for the alleviation of COVID-19-related pathologies

Abstract

The pandemic of COVID-19 caused worldwide concern. Due to the lack of appropriate medications and the inefficiency of commercially available vaccines, lots of efforts are being made to develop de novo therapeutic modalities. Besides this, the possibility of several genetic mutations in the viral genome has led to the generation of resistant strains such as Omicron against neutralizing antibodies and vaccines, leading to worsening public health status. Exosomes (Exo), nanosized vesicles, possess several therapeutic properties that participate in intercellular communication. The discovery and application of Exo in regenerative medicine have paved the way for the alleviation of several pathologies. These nanosized particles act as natural bioshuttles and transfer several biomolecules and anti-inflammatory cytokines. To date, several approaches are available for the administration of Exo into the targeted site inside the body, although the establishment of standard administration routes remains unclear. As severe acute respiratory syndrome coronavirus 2 primarily affects the respiratory system, we here tried to highlight the transplantation of Exo in the alleviation of COVID-19 pathologies.

Keywords: COVID-19; exosomes; paracrine interaction; regenerative potential; stem cell; therapeutic effects.

FIGURE 1

Mechanisms of SARS‐CoV‐2 entry into target cells. Using spike proteins (S1 and S2), this virus can fuse with the host cell membrane and inject genomic materials. ACE2, angiotensin‐converting enzyme 2; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2; TMPRSS2 and 4, transmembrane serine protease 2 and 4.

FIGURE 2

Exo biogenesis machinery system. These particles are produced using the endosomal system and several effectors. After the formation of early endosomes, the invagination of the vesicle membrane can produce numerous intraluminal vesicles (ILVs) which are attached. Multivesicular bodies are directed toward lysosomal degradation or formed late endosomes which can fuse with the plasma membrane and release ILVS into the ECM. ILVs hereafter are known as Exo. ECM, extracellular matrix; ESCRT, endosomal sorting complexes required for transport machinery; Exo, exosomes; MVBs, multivesicular bodies.

FIGURE 3

Different therapeutic effects of Exo in pulmonary tissue infected with SARS‐CoV‐2.  ACE2, angiotensin‐converting enzyme 2; bFGF, basic fibroblast growth factor; Exo, exosomes; ICAM‐1, intercellular adhesion molecule 1; IL‐6, interleukin‐6; iNOS, inducible nitric oxide synthase; ISG, interferon‐stimulated gene; PECAM, platelet endothelial cell adhesion molecule;ROS, reactive oxygen species; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2; TGF‐β, transforming growth factor β; TNF‐α, tumor necrosis factor α; VCAM‐1, vascular cell adhesion molecule 1; VEGF, vascular endothelial growth factor.