Mesenchymal Stem Cell-Derived Extracellular Vesicles Carrying miRNA as a Potential Multi Target Therapy to COVID-19: an In Silico Analysis

Abstract

In the end of 2019 COVID-19 emerged as a new threat worldwide and this disease present impaired immune system, exacerbated production of inflammatory cytokines, and coagulation disturbs. Mesenchymal stem cell (MSC) derived extracellular vesicles (EVs) have emerged as a therapeutic option due to its intrinsic properties to alleviate inflammatory responses, capable to promote the restoring of injured tissue. EVs contain heterogeneous cargo, including active microRNAs, small noncoding sequences involved in post-transcriptional gene repression or degradation and can attach in multiple targets. This study investigated whether the MSC-EVs miRNA cargo has the capacity to modulate the exacerbated cytokines, cell death and coagulation disturbs present in severe COVID-19. Through bioinformatics analysis, four datasets of miRNA, using different stem cell tissue sources (bone marrow, umbilical cord and adipose tissue), and one dataset of mRNA (bone marrow) were analyzed. 58 miRNAs overlap in the four miRNA datasets analyzed. Sequentially, those miRNAs present in at least two datasets, were analyzed using miRWalk for the 3'UTR binding target mRNA. The result predicted 258 miRNAs for exacerbated cytokines and chemokines, 266 miRNAs for cell death genes and 148 miRNAs for coagulation cascades. Some miRNAs may simultaneously attenuate inflammatory agents, inhibit cell death genes and key factors of coagulation cascade, consequently preventing tissue damage and coagulation disturbs. Therefore, the MSC-derived EVs due to their heterogeneous cargo are a potential multitarget approach able to improve the survival rates of severe COVID-19 patients.

Targeting the PANoptosome with miRNA Loaded Mesenchymal Stem Cell Derived Extracellular Vesicles; a New Path to Fight Against the Covid-19?

“…However, when these miRNAs are examined in detail, it is seen that there is no miRNA that collectively blocks the pathways of piroptosis, apoptosis and necroptosis. [27]. These reports provide hints that PANoptosis may be one of the factors that play a role in Covid-19 pathogenesis.…”

Mesenchymal stem cells and their derived exosomes to combat Covid–19

“… 85 In‐silico analysis has shown massive amount of various miRNA cargo in MSC‐Es, which includes 258 miRNAs related to cytokines and chemokines and 266 miRNAs for cell death (pyroptosis, apoptosis, and necrosis) genes. 86 Xiao and colleagues have demonstrated the downregulation of the Ikbkb gene results in a significant decrease in the gene expression of IKKβ, leading to downregulation of ubiquitin‐specific peptidase (Usp) 5, a deubiquitinase that blocks IKKβ ubiquitination. 82 There are a limited number of clinical trials ongoing to assess the safety and efficacy of MSC‐E for the treatment of Covid‐19, despite promising results in preclinical studies (Table 2 ).…”

Problems of Pathogenesis and Pathogenetic Therapy of COVID-19 from the Perspective of the General Theory of Pathological Systems (General Pathological Processes)

“…In the fight against the pandemic, protein target-oriented drug management is not less important, and various molecules have been presented as potential therapeutic options for SARS-CoV-2 (reviewed in [ 311 ]). Finally, several mesenchymal stem-cell-derived extracellular vesicles carrying miRNA due to their intrinsic properties to modulate the exacerbated cytokines, cell death, and coagulation disturbances present in severe COVID-19 were proposed as a potential multitarget therapy [ 312 ].…”