Mesenchymal stromal cells to fight SARS-CoV-2: Taking advantage of a pleiotropic therapy

Barros, Inês; Silva, António; Almeida, Luís Pereira de; Miranda, Catarina

doi:10.1016/j.cytogfr.2020.12.002

Cited by 21 publications

(19 citation statements)

References 144 publications

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“…Mesenchymal stem cells, also known as mesenchymal stromal cells (MSCs) ( Viswanathan et al, 2019 ), are heterogeneously multipotent stem cells that can be isolated from a variety of sources, including umbilical cord, human tissues like bone marrow and adipose tissue (using the stromal vascular fraction – SVF), and menstrual blood ( Blaber et al, 2012 ; Kallmeyer and Pepper, 2015 ; Elgaz et al, 2019 ; Copcu, 2020 ; Gentile and Sterodimas, 2020a , b ; Jeyaraman et al, 2020 ; Juárez-Navarro et al, 2020 ; Lin et al, 2020 ; Barros et al, 2021 ; Gentile, 2021 ; Mazini et al, 2021 ; Xu et al, 2021 ).…”

Section: Mesenchymal Stem Cell Transplantation In Covid-19 Patients: Rationale and Resultsmentioning

confidence: 99%

“…As suggested by successful MSC use in a number of pathological scenarios involving uncontrolled immune activation with consequent tissue damage, like for example H9N2 induced acute lung injury, ARDS, autoimmune diseases and graft-versus-host disease ( Waterman et al, 2010 ; Elgaz et al, 2019 ; Coelho et al, 2020 ; Yen et al, 2020 ; Barros et al, 2021 ; Musial and Gorska-Ponikowska, 2021 ; Su et al, 2021 ), the undeniable immunomodulatory and inflammation relieving properties of MSCs make them putative candidates as rejuvenating factors for the older immune system, on the basis of the documented ability to reduce pro-inflammatory mediators and to promote the expansion of regulatory lymphocyte subsets ( Yeo et al, 2021 ). Also, MSC transplantation can contribute to the amelioration of aging frailty ( Schulman et al, 2018 ; Florea et al, 2019 ; Sun et al, 2019 ), but MSC may exhibit age related deteriorating functions linked to inflammageing, especially in terms of alterations in number and characteristics of extracellular vesicles, DAMP production, excessive IL-6 release, loss of MSC ability to shift monocyte polarization toward M2, and triggering of ineffective hemopoiesis ( Tsuruhara et al, 2017 ; Lee and Yu, 2020 ).…”

Section: Mesenchymal Stem Cell Transplantation In Covid-19 Patients: Rationale and Resultsmentioning

confidence: 99%

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Immunopathology and Immunosenescence, the Immunological Key Words of Severe COVID-19. Is There a Role for Stem Cell Transplantation?

Ligotti

Pojero

Accardi

et al. 2021

Front. Cell Dev. Biol.

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The outcomes of Coronavirus disease-2019 (COVID-19) vary depending on the age, health status and sex of an individual, ranging from asymptomatic to lethal. From an immunologic viewpoint, the final severe lung damage observed in COVID-19 should be caused by cytokine storm, driven mainly by interleukin-6 and other pro-inflammatory cytokines. However, which immunopathogenic status precedes this “cytokine storm” and why the male older population is more severely affected, are currently unanswered questions. The aging of the immune system, i.e., immunosenescence, closely associated with a low-grade inflammatory status called “inflammageing,” should play a key role. The remodeling of both innate and adaptive immune response observed with aging can partly explain the age gradient in severity and mortality of COVID-19. This review discusses how aging impacts the immune response to the virus, focusing on possible strategies to rejuvenate the immune system with stem cell-based therapies. Indeed, due to immunomodulatory and anti-inflammatory properties, multipotent mesenchymal stem cells (MSCs) are a worth-considering option against COVID-19 adverse outcomes.

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Section: Mesenchymal Stem Cell Transplantation In Covid-19 Patients: Rationale and Resultsmentioning

confidence: 99%

Section: Mesenchymal Stem Cell Transplantation In Covid-19 Patients: Rationale and Resultsmentioning

confidence: 99%

Immunopathology and Immunosenescence, the Immunological Key Words of Severe COVID-19. Is There a Role for Stem Cell Transplantation?

Ligotti

Pojero

Accardi

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“… 20 , 28 , 29 , 30 In addition to the lung, other organs involved include the heart and presentations with Kawasaki syndrome, acute coronary syndrome, coagulopathies, myocarditis, the brain and cerebrovascular accidents (CVA’s) and focused areas of neuro‐inflammation and acute kidney and renal failure, the gut and gastrointestinal alterations, the liver and acute liver injury and hepatic dysfunction. 31 , 32 , 33 , 34 , 35 During infection, neutrophils, monocytes, and T cells are recruited to the site of infection by following the chemoattractant gradient of inflammatory chemokines and chemokines produced by infected cells. 36 Under severe conditions, lymphocyte and leukocyte counts decrease, whereas inflammation marker (C‐reactive protein), lactic dehydrogenase, proinflammatory cytokines and chemokines (interleukin (IL) 1β, IL‐6, IL‐7, IL‐2, tumor necrosis factor (TNF)α, granulocyte‐colony stimulating factor (GCSF), interferon gamma‐induced protein‐10 (CXCL10), and monocyte chemoattractant protein‐1) are elevated dramatically.…”

Section: Pathogenicity Of Sars‐cov‐2mentioning

confidence: 99%

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

dehbidi

Goodarzi

Azhdari

et al. 2021

Reviews in Medical Virology

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Summary Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is causing an ongoing pandemic of coronavirus disease 2019 (Covid‐19). Effective therapies are required for the treatment of patients with severe stages of the disease. Mesenchymal stem cells (MSCs) have been evaluated in numerous clinical trials, but present challenges, such as carcinogenic risk and special storage conditions, coupled with insufficient data about their mechanism of action. The majority of unique properties of MSCs are related to their paracrine activity and especially to their exosomes. The impact of MSCs‐derived exosomes (MSC‐Es) on complications of Covid‐19 has been investigated in several studies. MSC‐Es may improve some complications of Covid‐19 such as cytokine storm, acute respiratory distress syndrome (ARDS) and acute lung injury (ALI). Additionally, these exosomes can be evaluated as an applicable nano‐size carrier for antiviral therapeutic agents. Herein, we consider several potential applications of MSCs and their derived exosomes in the treatment of Covid‐19.

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“…From observations of IEIs in a XLP-2 mouse model, infection-induced inflammation and mortality can be prevented by using resolvin D or ex vivo-expanded Tregs without the need for antimicrobial agents [33,34], suggesting that similar approaches could be tested for their efficacy in controlling the persistent inflammation associated with COVID-19. Mesenchymal stem cells, characterized by their anti-inflammatory activities and Treg-inducing capacity, have also been used in a small number of COVID-19 patients, and respective clinical trials are ongoing [158].…”

Section: Therapeutic Implications For Covid-19mentioning

confidence: 99%

Infection‐induced inflammation from specific inborn errors of immunity to COVID‐19

Chen

Lai

2021

The FEBS Journal

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Inborn errors of immunity (IEIs) are a group of genetically defined disorders leading to defective immunity. Some IEIs have been linked to mutations of immune receptors or signaling molecules, resulting in defective signaling of respective cascades essential for combating specific pathogens. However, it remains incompletely understood why in selected IEIs, such as X‐linked lymphoproliferative syndrome type 2 (XLP‐2), hypo‐immune response to specific pathogens results in persistent inflammation. Moreover, mechanisms underlying the generation of anticytokine autoantibodies are mostly unknown. Recently, IEIs have been associated with coronavirus disease 2019 (COVID‐19), with a small proportion of patients that contract severe COVID‐19 displaying loss‐of‐function mutations in genes associated with type I interferons (IFNs). Moreover, approximately 10% of patients with severe COVID‐19 possess anti‐type I IFN‐neutralizing autoantibodies. Apart from IEIs that impair immune responses to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), SARS‐CoV‐2 encodes several proteins that suppress early type I IFN production. One primary consequence of the lack of type I IFNs during early SARS‐CoV‐2 infection is the increased inflammation associated with COVID‐19. In XLP‐2, resolution of inflammation rescued experimental subjects from infection‐induced mortality. Recent studies also indicate that targeting inflammation could alleviate COVID‐19. In this review, we discuss infection‐induced inflammation in IEIs, using XLP‐2 and COVID‐19 as examples. We suggest that resolving inflammation may represent an effective therapeutic approach to these diseases.

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Mesenchymal stromal cells to fight SARS-CoV-2: Taking advantage of a pleiotropic therapy

Cited by 21 publications

References 144 publications

Immunopathology and Immunosenescence, the Immunological Key Words of Severe COVID-19. Is There a Role for Stem Cell Transplantation?

Immunopathology and Immunosenescence, the Immunological Key Words of Severe COVID-19. Is There a Role for Stem Cell Transplantation?

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

Infection‐induced inflammation from specific inborn errors of immunity to COVID‐19

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