key: cord-0079171-5n02h5bq
authors: Bobis-Wozowicz, Sylwia; Marbán, Eduardo
title: Editorial: Extracellular Vesicles as Next Generation Therapeutics
date: 2022-05-12
journal: Front Cell Dev Biol
DOI: 10.3389/fcell.2022.919426
sha: 43d3c1e7efbf99c6da563c850e50f6ae8e3f9eaf
doc_id: 79171
cord_uid: 5n02h5bq

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Similarly, pro-regenerative activity another miRNA molecule contained in the EVs, was investigated by Sanchez-Sanchez et. al. They explored cardioprotective properties of hypoxia-stimulated mesenchymal stem cell (MSC)-derived EV-containing miR-4732-3p. Activity of this miRNA was demonstrated to promote angiogenesis and ameliorate fibrosis, both in vitro and in vivo, in a rat model of myocardial infarction.

EVs were shown not only to directly stimulate tissue-residing cells for regeneration, but also to modulate function of immune cells, which are the major players in tissue injury and resolution. With this respect, Peck et al. showed that introducing a specific molecule exerting immunomodulatory function in neutral fibroblasts, resulted in the production of EVs with enhanced immunomodulatory capacity. Specifically, they selected tryptophan 2,3-dioxygenase (TDO2), a target gene of canonical Wnt-β-catenin pathway. Applying TDO2-enriched EVs in an animal model of acute myocardial infarction, greatly improved heart function.

Another dimension of immunomodulatory activity of EVs was presented by Cochran and Kornbluth, in the context of fighting cancer. EVs isolated from immune cells-natural killer NK3.3 cell line, were shown to contain an array of cytotoxic enzymes, as well as variety of miRNAs associated with anti-tumor activity. In a cell killing assay, such EVs were able to inhibit proliferation and induce apoptosis in hematopoietic and non-hematopoietic tumor cell lines. Importantly, the observed effect was tumor cell specific, since normal cells remained unaffected.

With respect to tumor cells, however, it was shown that they produce EVs which promote tumor cell proliferation and metastasis, leading to tumor progression (Figure 1) . Such EVs can alter tumor microenvironment, allowing tumor cells to escape recognition and clearance by immune cells (Xu et al., 2018) . A summary of recent findings in the field of tumor-related EVs, with emphasis on oral squamous cell carcinoma (OSCC), is presented in a review by Lu et al. OSCC represents 90% of oral cancers and is associated with low survival rate, thus constitutes a serious health problem. One of novel treatment options for OSCC may constitute EV isolated from therapeutically-approved cells, such as MSCs.

Apart from tumor cells, pathological EVs can also be released during inflammation and they are involved in spreading pathogens. In the light of recent SARS-CoV-2 pandemic, which affected millions of individuals worldwide and resulted in the onset of COVID-19 disease, the contribution by Pironti et al., provides a timely discussion on the potential link between virus spreading via EV secretory pathway and cardiovascular manifestations of COVID-19. It has been investigated that COVID-19 disturbs the renin-angiotensin system, thereby exacerbating heart function. To improve heart condition, EVs derived from therapeutically beneficial cells, such as MSCs or cardiosphere-derived cells (CDCs), can be applied.

The Research Topic of EV engineering, to enhance their biological activity and improve targeting toward specific cell or tissue type is comprehensively discussed by Nazimek and Bryniarski. It is known that upon delivery to a living organism, EVs are rapidly cleared by phagocytes, which significantly reduces their therapeutic potential. As FIGURE 1 | Characteristics, bioengineering and role of extracellular vesicles (EVs) in health and disease. EVs contain bioactive cargo in the form of proteins, lipids and nucleic acids which exert biological effects on target cells and thereby influence their fate. To improve functionality and specificity of EVs, they can be engineered by surface modification and/or loading a specific therapeutic cargo. Native and modified EVs can be used as next-generation cell-free therapeutics to improve health. On the contrary, EVs released in pathological conditions by, e.g. cancer cells or infected cells, participate in disease spreading and progression.

Frontiers in Cell and Developmental Biology | www.frontiersin.org May 2022 | Volume 10 | Article 919426 presented by Nazimek et al., EVs co-incubation with antigen-specific antibodies and light chains induces their aggregation. This modification extends their stability in body fluids and allows their escape from urinary excretion. Moreover, EV decoration with a specific antibody can greatly enhance tissue targeting. These advancements may boost therapeutic potential of EVs and their applicability to treat human diseases. Concluding, this Research Topic provides the state-of-the-art of recent discoveries in the field of EVs and highlights the importance of further research needed to fully explore their therapeutic potential. Transferring this knowledge to clinical practice will be a milestone achievement in contemporary medicine.

Advances in Therapeutic Applications of Extracellular Vesicles

Extracellular Vesicles in Cancer -Implications for Future Improvements in Cancer Care

All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication. 

We thank all the authors who contributed their excellent work in this exciting Research Topic. Figure 1 was created with BioRender.com (agreement no. MX23VBPVQN).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.