Immunomodulation of Mesenchymal Stem Cells in Acute Lung Injury: From Preclinical Animal Models to Treatment of Severe COVID-19

Li, Ju‐Pi; Wu, Kang‐Hsi; Chao, Wan‐Ru; Lee, Yi‐Ju; Yang, Shun‐Fa; Chao, Yu‐Hua

doi:10.3390/ijms23158196

Cited by 14 publications

(4 citation statements)

References 64 publications

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“…The MSC-Mφ interplay has a pivotal role in lung injury combating inflammation and promoting injury resolution [ 66 , 71 , 72 , 95 , 111 , 167 ]. For tissue recovery, crucial effects include the dampening of inflammation, release of IL-10 by Mφs, and favourable effects of eicosapentaenoic acid (EPA) and its derivatives, resolvins (Rv- D1, E1, and E2) and protectins secreted by MSCs [ 125 ].…”

Section: Therapeutic Potential Of Msc-mφ Interaction and Lung Injury ...mentioning

confidence: 99%

Key Role of Mesenchymal Stromal Cell Interaction with Macrophages in Promoting Repair of Lung Injury

Jerkić

Szászi

Laffey

et al. 2023

IJMS

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Lung macrophages (Mφs) are essential for pulmonary innate immunity and host defense due to their dynamic polarization and phenotype shifts. Mesenchymal stromal cells (MSCs) have secretory, immunomodulatory, and tissue-reparative properties and have shown promise in acute and chronic inflammatory lung diseases and in COVID-19. Many beneficial effects of MSCs are mediated through their interaction with resident alveolar and pulmonary interstitial Mφs. Bidirectional MSC-Mφ communication is achieved through direct contact, soluble factor secretion/activation, and organelle transfer. The lung microenvironment facilitates MSC secretion of factors that result in Mφ polarization towards an immunosuppressive M2-like phenotype for the restoration of tissue homeostasis. M2-like Mφ in turn can affect the MSC immune regulatory function in MSC engraftment and tissue reparatory effects. This review article highlights the mechanisms of crosstalk between MSCs and Mφs and the potential role of their interaction in lung repair in inflammatory lung diseases.

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Section: Therapeutic Potential Of Msc-mφ Interaction and Lung Injury ...mentioning

confidence: 99%

Key Role of Mesenchymal Stromal Cell Interaction with Macrophages in Promoting Repair of Lung Injury

Jerkić

Szászi

Laffey

et al. 2023

IJMS

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“…ALI has received increased public attention since the onset of coronavirus disease 2019 (33). However, sepsis remains the main cause of ALI (34), rendering it the leading cause of death in patients with sepsis.…”

Section: Discussionmentioning

confidence: 99%

Quercetin alleviates lipopolysaccharide‑induced acute lung injury by inhibiting ferroptosis via the Sirt1/Nrf2/Gpx4 pathway

Deng,

Li,

et al. 2023

Int J Mol Med

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Acute lung injury (ALI) causes high morbidity and mortality rates in critically ill patients, and there are currently no effective therapeutic drugs. Ferroptosis is a newly discovered mode of regulated cell death that contributes to the progression of ALI. Quercetin possesses anti-inflammatory and antioxidant properties. However, whether quercetin can protect against lipopolysaccharide (LPS)-induced ALI by inhibiting ferroptosis and its underlying mechanisms remains unclear. The present study evaluated the protective effects of quercetin and underlying molecular mechanisms in LPS-induced ALI by establishing an ALI mouse model and an alveolar epithelial cell injury model via treatment of the mice or alveolar epithelial cells with LPS. Mouse lung injury was assessed by evaluating the histological lung injury score, bronchoalveolar lavage fluid cell count and inflammatory cytokine levels; alveolar epithelial cell injury was assessed by cell counting kit-8, lactate dehydrogenase and EDU assays; and ferroptosis was assessed by detecting the changes in the levels of malondialdehyde, glutathione, iron, glutathione peroxidase 4 (Gpx4) and 4-hydroxynonenal in vivo and vitro. The present study indicated that quercetin effectively ameliorated LPS-induced ALI in the mouse model by reducing histopathological changes, proinflammatory cytokine release and reactive oxygen species generation and inhibiting ferroptosis. Quercetin significantly decreased ferroptosis and improved the proliferative ability of LPS-treated alveolar epithelial cells. Additionally, it was demonstrated that quercetin markedly enhanced the alveolar epithelial barrier, as evidenced by the upregulation of tight junction protein expression both in vivo and in vitro. Mechanistically, quercetin effectively activated the sirtuin 1 (Sirt1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/Gpx4 signaling pathway, and targeted in vivo inhibition or in vitro knockdown of Sirt1 significantly reduced the anti-ferroptotic functions of quercetin. In conclusion, the results demonstrated that quercetin exerts its therapeutic effects against LPS-induced ALI by inhibiting ferroptosis via the activation of the Sirt1/Nrf2/Gpx4 signaling pathway.

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“…Positive effects in terms of reducing pulmonary edema and inflammation and improving gas exchange have been reported after cell treatment in experimentally induced ARDS in sheep ( 22 , 25 , 32 , 36 , 37 ). Currently, research on the effect of SC on the treatment of ARDS caused by respiratory viruses is particularly relevant due to the COVID-19 pandemic ( 67 , 90 , 92 ). Reductions in oxidative stress and inflammation and resulting lung injury and mortality following treatment with SC have been observed in mice ( 13 , 17 , 19 , 21 ), rabbits ( 15 , 16 ) and dogs ( 33 ) with experimentally induced lung injury.…”

Section: Most Probable Therapeutic Application In Animalsmentioning

confidence: 99%

Regenerative medicine in lung diseases: A systematic review

Adamič

Vengušt²

2023

Front. Vet. Sci.

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Regenerative medicine has opened the door to the exploration of new therapeutic methods for the treatment of various diseases, especially those associated with local or general disregulation of the immune system. In pulmonary diseases, new therapeutic strategies have emerged that are aimed at restoring functional lung tissue rather than alleviating symptoms. These strategies focus on tissue regeneration using stem cells and/or their derivatives or replacement of dysfunctional tissue using biomedical engineering. Animal health can directly benefit from regenerative therapy strategies and also serve as a translational experimental model for human disease. Several clinical trials have been conducted to evaluate the effects of cellular treatment on inflammatory lung disease in animals. Data reported to date show several beneficial effects in ex vivo and in vivo models; however, our understanding of the mechanisms that regenerative therapies exert on diseased tissues remains incomplete.

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Immunomodulation of Mesenchymal Stem Cells in Acute Lung Injury: From Preclinical Animal Models to Treatment of Severe COVID-19

Cited by 14 publications

References 64 publications

Key Role of Mesenchymal Stromal Cell Interaction with Macrophages in Promoting Repair of Lung Injury

Key Role of Mesenchymal Stromal Cell Interaction with Macrophages in Promoting Repair of Lung Injury

Quercetin alleviates lipopolysaccharide‑induced acute lung injury by inhibiting ferroptosis via the Sirt1/Nrf2/Gpx4 pathway

Regenerative medicine in lung diseases: A systematic review

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