Mesenchymal stem cell (MSc) secretome: A possible therapeutic strategy for intensive-care COVID-19 patients

Deffune, Elenice; Prudenciatti, Aruã Mastrangelo; Moroz, Andrei

doi:10.1016/j.mehy.2020.109769

Cited by 25 publications

(24 citation statements)

References 12 publications

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“…Important roles for EVs have been implicated in oral mucosa and wound healing [ 97 ], intestinal inflammation and repair [ 98 ], host–pathogen interactions in intestinal infections [ 99 ], including via PAD-mediated pathways [ 69 ], and in intestinal mucosal immunity [ 100 ], as well as in airway tissue, lung disease and in allergic response [ 101 , 102 , 103 , 104 ]. Indeed, the regulation of EVs, their use as biomarkers and their application in the therapeutic intervention of COVID-19, have all recently been highlighted [ 61 , 62 , 63 , 105 , 106 , 107 ]. Therefore, the contribution of the different PAD isozymes in the regulation of EV release, also relating to tissue-specific PAD expression, will need to be explored in relation to SARS-CoV-2 infection in future in-depth studies.…”

Section: Discussionmentioning

confidence: 99%

“…PADs have also been identified as key regulators of cellular extracellular vesicle (EV) release [ 23 , 54 , 55 , 56 ], which is a central factor in many pathologies, including infections [ 20 , 57 , 58 , 59 , 60 ]. EV-mediated responses have therefore received a great deal of interest in COVID-19 [ 61 , 62 , 63 ], particularly seeing as EV signatures can be useful biomarkers [ 64 , 65 ]. PAD are conserved throughout the phylogenetic tree [ 15 , 41 ], and both PADs and their deiminated protein products are detected in a range of taxa [ 24 , 25 , 41 , 43 , 45 , 46 , 47 , 48 , 66 , 67 ], including in bacteria [ 39 ], fungi [ 68 ] and parasites [ 69 ], with some pathogens using their PAD homologues for immune evasion [ 70 ].…”

Section: Introductionmentioning

confidence: 99%

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Putative Roles for Peptidylarginine Deiminases in COVID-19

Arısan

Uysal-Onganer

Lange

2020

IJMS

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Peptidylarginine deiminases (PADs) are a family of calcium-regulated enzymes that are phylogenetically conserved and cause post-translational deimination/citrullination, contributing to protein moonlighting in health and disease. PADs are implicated in a range of inflammatory and autoimmune conditions, in the regulation of extracellular vesicle (EV) release, and their roles in infection and immunomodulation are known to some extent, including in viral infections. In the current study we describe putative roles for PADs in COVID-19, based on in silico analysis of BioProject transcriptome data (PRJNA615032 BioProject), including lung biopsies from healthy volunteers and SARS-CoV-2-infected patients, as well as SARS-CoV-2-infected, and mock human bronchial epithelial NHBE and adenocarcinoma alveolar basal epithelial A549 cell lines. In addition, BioProject Data PRJNA631753, analysing patients tissue biopsy data (n = 5), was utilised. We report a high individual variation observed for all PADI isozymes in the patients’ tissue biopsies, including lung, in response to SARS-CoV-2 infection, while PADI2 and PADI4 mRNA showed most variability in lung tissue specifically. The other tissues assessed were heart, kidney, marrow, bowel, jejunum, skin and fat, which all varied with respect to mRNA levels for the different PADI isozymes. In vitro lung epithelial and adenocarcinoma alveolar cell models revealed that PADI1, PADI2 and PADI4 mRNA levels were elevated, but PADI3 and PADI6 mRNA levels were reduced in SARS-CoV-2-infected NHBE cells. In A549 cells, PADI2 mRNA was elevated, PADI3 and PADI6 mRNA was downregulated, and no effect was observed on the PADI4 or PADI6 mRNA levels in infected cells, compared with control mock cells. Our findings indicate a link between PADI expression changes, including modulation of PADI2 and PADI4, particularly in lung tissue, in response to SARS-CoV-2 infection. PADI isozyme 1–6 expression in other organ biopsies also reveals putative links to COVID-19 symptoms, including vascular, cardiac and cutaneous responses, kidney injury and stroke. KEGG and GO pathway analysis furthermore identified links between PADs and inflammatory pathways, in particular between PAD4 and viral infections, as well as identifying links for PADs with a range of comorbidities. The analysis presented here highlights roles for PADs in-host responses to SARS-CoV-2, and their potential as therapeutic targets in COVID-19.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Putative Roles for Peptidylarginine Deiminases in COVID-19

Arısan

Uysal-Onganer

Lange

2020

IJMS

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“…59,[153][154][155][156][157][158][159][160][161] Regarding COVID-19, reports involving EVs are still rare. [162][163][164][165] However, a similar role of exosomes and MVs is assumed in COVID-19 as other virus infectious diseases. [166][167][168][169][170] In particular, concerning thrombosis, there is no doubt that COVID-19 causes more symptoms in comparison with the past virus infectious disease.…”

Section: Evs and Coagulatory Abnormalities During Viral Infectionmentioning

confidence: 94%

<p>Extracellular Vesicle-Related Thrombosis in Viral Infection</p>

Nomura

Taniura²,

Ito

2020

IJGM

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Although the outcomes of viral infectious diseases are remarkably varied, most infections cause acute diseases after a short period. Novel coronavirus disease 2019, which recently spread worldwide, is no exception. Extracellular vesicles (EVs) are small circulating membrane-enclosed entities shed from the cell surface in response to cell activation or apoptosis. EVs transport various kinds of bioactive molecules between cells, including functional RNAs, such as viral RNAs and proteins. Therefore, when EVs are at high levels, changes in cell activation, inflammation, angioplasty and transportation suggest that EVs are associated with various diseases. Clinical research on EVs includes studies on the coagulatory system. In particular, abnormal enhancement of the coagulatory system through EVs can cause thrombosis. In this review, we address the functions of EVs, thrombosis, and their involvement in viral infection.

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“…During infection, EVs can amplify inflammation and deflagrate antiviral responses (Urbanelli et al, 2019) and can also mediate communication between immune cells and other cell types (Isola and Chen, 2017). The involvement of EVs in viral infection and/or host interactions in disease has already been described for several viruses, such as rabies (Wang et al, 2019b), coronaviruses (Maeda et al, 1999;Kuate et al, 2007;Börger et al, 2020;Deffune et al, 2020;Hassanpour et al, 2020;Inal, 2020a;Inal, 2020b;Kumar et al, 2020;O'Driscoll, 2020;Tsuchiya et al, 2020;Urciuoli and Peruzzi, 2020), HCV (Bartosch et al, 2003;Timpe et al, 2008;Dreux et al, 2012;Bukong et al, 2014), HBV (Jia et al, 2017;, HIV (Princen et al, 2004;Khatua et al, 2009;Xu et al, 2009;Lenassi et al, 2010;Bernard et al, 2014;Raymond et al, 2016;Sampey et al, 2016;Kodidela et al, 2018;Haque et al, 2020;Ranjit et al, 2020), HPV (Honegger et al, 2015;Guenat et al, 2017;Sadri Nahand et al, 2019;Chiantore et al, 2020), HSV (Temme et al, 2010;Han et al, 2016;Deschamps and Kalamvoki, 2018) dengue (Martins et al, 2018;…”

Section: Evs In Immune Communication and Cytokine Responses During Inmentioning

confidence: 98%

Extracellular Vesicles in Viral Infections: Two Sides of the Same Coin?

Martins

Alves

2020

Front. Cell. Infect. Microbiol.

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Extracellular vesicles are small membrane structures containing proteins and nucleic acids that are gaining a lot of attention lately. They are produced by most cells and can be detected in several body fluids, having a huge potential in therapeutic and diagnostic approaches. EVs produced by infected cells usually have a molecular signature that is very distinct from healthy cells. For intracellular pathogens like viruses, EVs can have an even more complex function, since the viral biogenesis pathway can overlap with EV pathways in several ways, generating a continuum of particles, like naked virions, EVs containing infective viral genomes and quasi-enveloped viruses, besides the classical complete viral particles that are secreted to the extracellular space. Those particles can act in recipient cells in different ways. Besides being directly infective, they also can prime neighbor cells rendering them more susceptible to infection, block antiviral responses and deliver isolated viral molecules. On the other hand, they can trigger antiviral responses and cytokine secretion even in uninfected cells near the infection site, helping to fight the infection and protect other cells from the virus. This protective response can also backfire, when a massive inflammation facilitated by those EVs can be responsible for bad clinical outcomes. EVs can help or harm the antiviral response, and sometimes both mechanisms are observed in infections by the same virus. Since those pathways are intrinsically interlinked, understand the role of EVs during viral infections is crucial to comprehend viral mechanisms and respond better to emerging viral diseases.

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Mesenchymal stem cell (MSc) secretome: A possible therapeutic strategy for intensive-care COVID-19 patients

Cited by 25 publications

References 12 publications

Putative Roles for Peptidylarginine Deiminases in COVID-19

Putative Roles for Peptidylarginine Deiminases in COVID-19

<p>Extracellular Vesicle-Related Thrombosis in Viral Infection</p>

Extracellular Vesicles in Viral Infections: Two Sides of the Same Coin?

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