Therapeutic potential of mesenchymal stem cells and their exosomes in severe novel coronavirus disease 2019 (COVID-19) cases

Tsuchiya, Atsunori; Takeuchi, Suguru; Iwasawa, Takahiro; Kumagai, Motoki; Toshihiko, Sato; Motegi, Satoko; Ishii, Yui; Koseki, Youhei; Tomiyoshi, Kei; Natsui, Kazuki; Takeda, Nobutaka; Yoshida, Yuki; Yamazaki, Fusako; Kojima, Yuichi; Watanabe, Yusuke; Kimura, Naruhiro; Tominaga, Kentaro; Kamimura, Hiroteru; Takamura, Masaaki; Terai, Shuji

doi:10.1186/s41232-020-00121-y

Cited by 68 publications

(78 citation statements)

References 42 publications

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“…More recently, MSCs have been tested for the treatment of coronavirus disease 2019 (COVID-19) [4]. At present, there are two registered studies examining MSC-derived extracellular vesicles (MSC-EVs) as a candidate for treating severe COVID-19 (NCT04491240, NCT04276987) [5]. The beneficial effects of MSCs were originally attributed to their ability to home to the damaged tissues and differentiate into many cell types.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cell-derived extracellular vesicles alter disease outcomes via endorsement of macrophage polarization

et al. 2020

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Mesenchymal stem cells (MSCs) are adult stromal cells that reside in virtually all postnatal tissues. Due to their regenerative and immunomodulatory capacities, MSCs have attracted growing attention during the past two decades. MSC-derived extracellular vesicles (MSC-EVs) are able to duplicate the effects of their parental cells by transferring functional proteins and genetic materials to recipient cells without cell-to-cell contact. MSC-EVs also target macrophages, which play an essential role in innate immunity, adaptive immunity, and homeostasis. Recent studies have demonstrated that MSC-EVs reduce M1 polarization and/or promote M2 polarization in a variety of settings. In this review, we discuss the mechanisms of macrophage polarization and roles of MSC-EV-induced macrophage polarization in the outcomes of cardiovascular, pulmonary, digestive, renal, and central nervous system diseases. In conclusion, MSC-EVs may become a viable alternative to MSCs for the treatment of diseases in which inflammation and immunity play a critical role.

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Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cell-derived extracellular vesicles alter disease outcomes via endorsement of macrophage polarization

et al. 2020

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“…However, because the cytokine storm is found predominantly in COVID-19 patients, it is essential to consider drugs that inhibit viral replication while treating the cytokine storm. Hence, MSC-Exos may be appropriate therapeutic agents for COVID-19 (97). MSCs can be more advantageous than other anti-inflammatory agents, because they can provide immunomodulatory effects based on the host cells.…”

Section: Future Directionsmentioning

confidence: 99%

Immunomodulatory effect of mesenchymal stem cells and mesenchymal stem-cell-derived exosomes for COVID-19 treatment

et al. 2020

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The world has witnessed unimaginable damage from the coronavirus disease-19 (COVID-19) pandemic. Because the pandemic is growing rapidly, it is important to consider diverse treatment options to effectively treat people worldwide. Since the immune system is at the hub of the infection, it is essential to regulate the dynamic balance in order to prevent the overexaggerated immune responses that subsequently result in multiorgan damage. The use of stem cells as treatment options has gained tremendous momentum in the past decade. The revolutionary measures in science have brought to the world mesenchymal stem cells (MSCs) and MSC-derived exosomes (MSC-Exo) as therapeutic opportunities for various diseases. The MSCs and MSC-Exos have immunomodulatory functions; they can be used as therapy to strike a balance in the immune cells of patients with COVID-19. In this review, we discuss the basics of the cytokine storm in COVID-19, MSCs, and MSC-derived exosomes and the potential and stem-cell-based ongoing clinical trials for COVID-19. [BMB Reports 2020; 53(8): 400-412]

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“…Recent reviews have described the potential for and rationale of using different types of MSCs for treating severe COVID-19 patients to protect alveolar epithelial cells, to reclaim the pulmonary microenvironment, to induce anti-inflammatory macrophages, regulatory T and B cells, and regulatory dendritic cells. In addition, MSCs can inactivate T cells in order to prevent cytokine storm, prevent pulmonary fibrosis and cure lung dysfunction[ 101 - 104 ]. Details of MSCs clinical trials for COVID-19 have also been discussed in other reviews[ 101 , 104 - 106 ].…”

Section: Recent Success Of Mscs For Covid-19 Patients and Clinical Trmentioning

confidence: 99%

“…In addition, MSCs can inactivate T cells in order to prevent cytokine storm, prevent pulmonary fibrosis and cure lung dysfunction[ 101 - 104 ]. Details of MSCs clinical trials for COVID-19 have also been discussed in other reviews[ 101 , 104 - 106 ].…”

Section: Recent Success Of Mscs For Covid-19 Patients and Clinical Trmentioning

confidence: 99%

Mesenchymal stem cells as living anti-inflammatory therapy for COVID-19 related acute respiratory distress syndrome

Lin¹,

Ichim²,

Pingle³

et al. 2020

WJSC

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Coronavirus disease 2019 (COVID-19), a pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), is growing at an exponential rate worldwide. Manifestations of this disease are heterogeneous; however, advanced cases often exhibit various acute respiratory distress syndrome-like symptoms, systemic inflammatory reactions, coagulopathy, and organ involvements. A common theme in advanced COVID-19 is unrestrained immune activation, classically referred to as a “cytokine storm”, as well as deficiencies in immune regulatory mechanisms such as T regulatory cells. While mesenchymal stem cells (MSCs) themselves are objects of cytokine regulation, they can secrete cytokines to modulate immune cells by inducing anti-inflammatory regulatory Treg cells, macrophages and neutrophils; and by reducing the activation of T and B cells, dendritic and nature killer cells. Consequently, they have therapeutic potential for treating severe cases of COVID-19. Here we discuss the unique ability of MSCs, to act as a “living anti-inflammatory”, which can “rebalance” the cytokine/immune responses to restore equilibrium. We also discuss current MSC trials and present different concepts for optimization of MSC therapy in patients with COVID-19 acute respiratory distress syndrome.

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Therapeutic potential of mesenchymal stem cells and their exosomes in severe novel coronavirus disease 2019 (COVID-19) cases

Cited by 68 publications

References 42 publications

Mesenchymal stem cell-derived extracellular vesicles alter disease outcomes via endorsement of macrophage polarization

Mesenchymal stem cell-derived extracellular vesicles alter disease outcomes via endorsement of macrophage polarization

Immunomodulatory effect of mesenchymal stem cells and mesenchymal stem-cell-derived exosomes for COVID-19 treatment

Mesenchymal stem cells as living anti-inflammatory therapy for COVID-19 related acute respiratory distress syndrome

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