Immunoregulatory Effects of Stem Cell-Derived Extracellular Vesicles on Immune Cells

Xie, Min; Wang, Xiong; She, Zhou; Wen, Zaichi; Abdirahman, Amin Sheikh; Wan, Wuqing; Wen, Chuan

doi:10.3389/fimmu.2020.00013

Cited by 79 publications

(67 citation statements)

References 122 publications

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“…During tumor progression, EVs derived from different cells (tumor cells, stromal cells, immune cells, etc.) play an important role and participate in the formation of TME [44,[52][53][54].…”

Section: The Biosynthesis and Function Of Extracellular Vesicles And mentioning

confidence: 99%

Exosomal miRNAs in tumor microenvironment

Tan

Xia

et al. 2020

J Exp Clin Cancer Res

120

117

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Tumor microenvironment (TME) is the internal environment in which tumor cells survive, consisting of tumor cells, fibroblasts, endothelial cells, and immune cells, as well as non-cellular components, such as exosomes and cytokines. Exosomes are tiny extracellular vesicles (40-160nm) containing active substances, such as proteins, lipids and nucleic acids. Exosomes carry biologically active miRNAs to shuttle between tumor cells and TME, thereby affecting tumor development. Tumor-derived exosomal miRNAs induce matrix reprogramming in TME, creating a microenvironment that is conducive to tumor growth, metastasis, immune escape and chemotherapy resistance. In this review, we updated the role of exosomal miRNAs in the process of TME reshaping.

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Section: The Biosynthesis and Function Of Extracellular Vesicles And mentioning

confidence: 99%

Exosomal miRNAs in tumor microenvironment

Tan

Xia

et al. 2020

J Exp Clin Cancer Res

120

117

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“…MVs mostly contain mRNAs, microRNAs, cytokines, and chemokines that can regulate a wide number of biological processes, including the function and homing of immune cells[ 121 , 122 ]. It has been shown that MVs derived from BM-MSCs suppress the expression of IL-1β and TNF-α and can promote the conversion of Th1 to Th2 responses[ 120 , 123 ]. Also, MVs contain the miRNAs miR-145, miR-146, and miR-155, which can effectively suppress the expression of TNF receptor-associated factor 6 and IL-1 receptor-associated kinase 1, followed by down-regulation of NF-κB p65 phosphorylation[ 120 , 122 , 124 ].…”

Section: Mscs and Covid-19mentioning

confidence: 99%

Mesenchymal stromal cells as potential immunomodulatory players in severe acute respiratory distress syndrome induced by SARS-CoV-2 infection

Mallis¹,

Michalopoulos²,

Chatzistamatiou³

et al. 2020

WJSC

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Severe acute respiratory syndrome coronavirus-2 and the related coronavirus disease-19 (COVID-19) is a worldwide emerging situation, which was initially reported in December 2019 in Wuhan, China. Currently, more than 7258842 new cases, and more than 411879 deaths have been reported globally. This new highly transmitted coronavirus is responsible for the development of severe acute respiratory distress syndrome. Due to this disorder, a great number of patients are hospitalized in the intensive care unit followed by connection to extracorporeal membrane oxygenation for breath supporting and survival. Severe acute respiratory distress syndrome is mostly accompanied by the secretion of proinflammatory cytokines, including interleukin (IL)-2, IL-6, IL-7, granulocyte colony-stimulating factor (GSCF), interferon-inducible protein 10 (IP10), monocyte chemotactic protein-1 (MCP1), macrophage inflammatory protein 1A (MIP1A), and tumor necrosis factor alpha (TNF-α), an event which is known as “cytokine storm”. Further disease pathology involves a generalized modulation of immune responses, leading to fatal multiorgan failure. Currently, no specific treatment or vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been developed. Mesenchymal stromal cells (MSCs), which are known for their immunosuppressive actions, could be applied as an alternative co-therapy in critically-ill COVID-19 patients. Specifically, MSCs can regulate the immune responses through the conversion of Th1 to Th2, activation of M2 macrophages, and modulation of dendritic cells maturation. These key immunoregulatory properties of MSCs may be exerted either by produced soluble factors or by cell-cell contact interactions. To date, several clinical trials have been registered to assess the safety, efficacy, and therapeutic potential of MSCs in COVID-19. Moreover, MSC treatment may be effective for the reversion of ground-glass opacity of damaged lungs and reduce the tissue fibrosis. Taking into account the multifunctional properties of MSCs, the proposed stem-cell-based therapy may be proven significantly effective in critically-ill COVID-19 patients. The current therapeutic strategy may improve the patient’s overall condition and in parallel may decrease the mortality rate of the current disease.

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“…Because they are essentially liposomes, EVs are simple biological structures that are more stable in vivo than other particles [43]. Moreover, EVs invade host cells directly through membrane fusion, receptor-mediated phagocytosis, and other internalization mechanisms, which contribute to physiological and pathological processes such as activation of signaling pathways and immune responses [44]. Taken together, the observations reported herein suggest that MSC-EVs are an effective antiviral treatment.…”

Section: Discussionmentioning

confidence: 58%

Antiviral effects of miRNAs in extracellular vesicles against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mutations in SARS-CoV-2 RNA virus

Park

Choi

Lim

et al. 2020

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus 2019 (COVID-19). No treatment is available. Micro-RNAs (miRNAs) in mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are potential novel therapeutic agents because of their ability to regulate gene expression by inhibiting mRNA. Thus, they may degrade the RNA genome of SARS-CoV-2. EVs can transfer miRNAs to recipient cells and regulate conditions within them. MSC-EVs harbor major therapeutic miRNAs that play important roles in the biological functions of virus-infected host cells. Here, we examined their potential impact on viral and immune responses. MSC-EVs contained 18 miRNAs predicted to interact directly with the 3’ UTR of SARS-CoV-2. These EVs suppressed SARS-CoV-2 replication in Vero E6 cells. In addition, five major miRNAs suppressed virus activity in a luciferase reporter assay by binding the 3’ UTR. MSC-EVs showed strong regenerative effects and potent anti-inflammatory activity which may prevent lethal cytokine storms. We confirmed that EVs regulated inflammatory responses by several cell types, including human brain cells that express the viral receptor ACE2, suggesting that the brain may be targeted by SARS-CoV-2. miRNAs in MSC-EVs have several advantages as therapeutic agents against SARS-CoV-2: 1) they bind specifically to the viral 3’ UTR, and are thus unlikely to have side effects; 2) because the 3’ UTR is highly conserved and rarely mutates, MSC-EV miRNAs could be used against novel variants arising during viral replication; and 3) unique cargoes carried by MSC-EVs can have diverse effects, such as regenerating damaged tissue and regulating immunity.

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Immunoregulatory Effects of Stem Cell-Derived Extracellular Vesicles on Immune Cells

Cited by 79 publications

References 122 publications

Exosomal miRNAs in tumor microenvironment

Exosomal miRNAs in tumor microenvironment

Mesenchymal stromal cells as potential immunomodulatory players in severe acute respiratory distress syndrome induced by SARS-CoV-2 infection

Antiviral effects of miRNAs in extracellular vesicles against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mutations in SARS-CoV-2 RNA virus

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