Exosomal Biomarkers: Roles in Diagnostics and Therapeutics

In this Research Topic, Twelve articles were accepted by the Frontiers Editorial team and included Original Research, Reviews, Mini-Reviews, and perspectives in the advancement of exosome and exosome-based diagnostics, non-invasive biopsy, and therapeutic approaches. The articles submitted were of high quality and add to new information in this fast growing area of research with futuristic approach towards non-invasive diagnosis and novel therapeutic strategies.. In a search for surface or surface associated proteins on Extracellular Vesicles (EVs) to serve as diagnostic biomarkers, the research group of Moller Jorgensen (Lee-Ann Clegg et al) developed a simple and elegant multi-parametric microarray-based procedure termed EV Array that allows measurement of multiple EV marker proteins in a single analysis. This method uses extremely low amounts of body fluids directly obviating any time-consuming tedious purification protocols. The authors say their method is being used in hospitals of the Aalborg University for several clinical diagnostic and prognostic studies with diseases as lung cancers, multiple sclerosis and atrial fibrillation. Certainly, investigators will find the EV array procedure helpful in assessing, if any, the expression of EV markers in clinical situations and quick diagnosis.A research group led by Liu Xuehong and Ye Jingyao selected a unique topic within the area of EV research and presented an interesting review on the roles of macrophage-derived extracellular vesicles (EVs) in multisystem diseases, with particular focus on cancers, cardiovascular diseases, inflammatory diseases, and Osteo-related pathologies. Another interesting part proposed in this review is the bioengineering of macrophage-EVs and their usefulness as biomarkers in disease diagnosis and treatment.Another group of Gulati et al reviewed published research suggesting theranostic applications of exosomes in malignancies and possible help in assessing clinical prognosis of aggressive Cancers. The authors also reviewed role of exosomes in various signaling mechanisms like angiogenesis and tumor metastasis, immuno-editing, and drug resistance.Yet in another article, Likewise, Zhang et al review the latest advances of EVs as prognostic and diagnostic biomarkers, and therapeutic agents and discuss specific diagnostic or therapeutic application of EVs as a novel drug delivery vehicle and their application in therapy of Cardio Vascular Diseases.. The authors also discuss the perspectives, challenges, and applications on EVs' clinical and industrial transformation.There was an interesting submission on the role of exosomes in Covid-19. With the emergence of the new SARS-CoV-2 virus in late 2019 that affected lives worldwide including pregnant women, the group of Y Singh( Cao et al) have inquired what different approaches in relation to prevention, diagnostics and therapeutics were available. They investigated how COVID-19 affected the exosomes production in pregnant women recovered from the pandemic and how these exosomes regulate the adaptive immune response. In their study the authors observed several exosomal markers including CD9, CD31, CD40, CD45, CD41b, CD42a, CD62P, CD69, CD81, CD105 and HLA-DRDPDQ in the plasma of COVID-19 recovered pregnant women to be significantly less abundant compared with a control group and thus Covid-19 recovered pregnant women possessed less immunogenic properties.The group of Li et al, while investigating the function of exosomal PCAT6 in vascular endothelial cell development, identified the exosomal lncRNA, PCAT6, with high expression level in characterized patients with sufficient coronary collateral artery function. In mechanical investigation, PCAT6 was able to target BRD4 in the endothelial cells. The BRD4 overexpression and miR-139-3p inhibitor could reverse down-regulated PCAT6-mediated suppression of endothelial cells. Functionally, the depletion of exosomal PCAT6 significantly inhibited the growth of endothelial cells in vitro. Their findings that exosomal PCAT6 regulates the biological behaviors of endothelial cells by miR-139-3p/BRD4 axis suggests that exosomal PCAT6 could prove to be suitable biomarker for discriminating between patients with gooddeveloped or poorly developed collaterals. Moreover, as PCAT6 regulates arteriogenesis, it is easy to detect and can serve as potential therapeutic target for ischemic disease.Xiaofei Feng et al studied a complex multifactorial disease model, Intervertebral disc (IVD) degeneration, with ill-defined pathogenesis. They inquired whether exosomes derived from degenerative nucleus pulposus (NP)cells promoteapoptosis of cartilage endplate (CEP) cells and aggravate IVD degeneration, there being few studies on the information interaction. between NPCs and CEPCs.. Their study demonstrated that degenerated NPC-exosome could induce apoptosis of CEPCs, inhibit ECM synthesis, and promote ECM degradation. In addition, it was proved that degenerated NPC-exosome aggravates IVD degeneration.Ye Zeng et al in their excellent review discuss the advantages and the challenges associated with the application of Extracellular Vesicles(EVs) which are now known to be involved in a variety of pathophysiological processes in many diseases. They also discuss the resolution of shortcomings experienced in isolation and purification methods, storage conditions and pharmacokinetics and bio-distribution patterns during drug delivery which will certainly facilitate the clinical application of EVs. However, due to size differences and lack of specific markers, the EVs as well as exosomal preparations are heterogeneous with questionable purity and origin, a position term by International Society of Extracellular Vesicles, Gothenburg( Switzerland), a better expression be EVs and not Exosomes be adopted, though these terms are used interchangeably by several groups.Finally, a group of Zeng-Hong Wu reports inquires in their bioinformatics based study on the diagnostic application of exosomes in Hepatocellular carcinoma (HCC), globally considered as the fifty most common cancer with a high mortality rate and second most common cause among cancer-related deaths. The researchers accessed exosome data from exoRBase database and a free online database to estimate possible binding miRNA from mRNA, lncRNA, and circRNA and examine useful exosome biomarkers for HCC therapy. Their transcriptome study using Cytoscape revealed 159 mRNAs, 60 lncRNAs, and 13 circRNAs to be differentially expressed and identified MARCH8, SH3PXD2A, has-circ-0014088, hsa-miR-186-5p, and hsa-miR-613 as hub biomarkers. Their KEGG pathway analytics demonstrated the differentially expressed proteins to be principally involved in the MAPK signaling network, central carbon metabolism in cancer, the glucagon signaling pathway, glutamatergic synapse, and spliceosome. The Human Protein Atlas (HPA) online tool evaluating the protein expression of SMARCA5, CDC42, and UBC between normal and cancer tissues showed that these three genes expression were significantly up regulated in tumor tissues. This could mimic exosome microenvironmental disorders providing potential biomarkers for exosome for therapeutic applications