Advances in mesenchymal stromal cell therapy for acute lung injury/acute respiratory distress syndrome

Liu, Chang; Xiao, Kun; Xie, Lixin

doi:10.3389/fcell.2022.951764

Cited by 3 publications

(2 citation statements)

References 212 publications

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“…This clearly precludes the immediate use of MSCs in lung diseases, even though novel therapeutic approaches are desperately needed. More critically, there is no effective treatment for ARDS, a condition that develops and progresses rapidly and has high mortality [ 200 ]. For this reason, most of the clinical studies exploring the use of MSCs or their derivatives are conducted in ARDS patients [ 200 , 201 ].…”

Section: Discussionmentioning

confidence: 99%

“…More critically, there is no effective treatment for ARDS, a condition that develops and progresses rapidly and has high mortality [ 200 ]. For this reason, most of the clinical studies exploring the use of MSCs or their derivatives are conducted in ARDS patients [ 200 , 201 ]. However, these studies were carried out with a relatively small number of enrolled patients.…”

Section: Discussionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Jerkić

Szászi

Laffey

et al. 2023

IJMS

View full text Add to dashboard Cite

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Manufacturing, quality control, and GLP-grade preclinical study of nebulized allogenic adipose mesenchymal stromal cells-derived extracellular vesicles

Wang,

Chen,

Zhang

et al. 2024

Stem Cell Res Ther

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Background Human adipose stromal cells-derived extracellular vesicles (haMSC-EVs) have been shown to alleviate inflammation in acute lung injury (ALI) animal models. However, there are few systemic studies on clinical-grade haMSC-EVs. Our study aimed to investigate the manufacturing, quality control (QC) and preclinical safety of clinical-grade haMSC-EVs. Methods haMSC-EVs were isolated from the conditioned medium of human adipose MSCs incubated in 2D containers. Purification was performed by PEG precipitation and differential centrifugation. Characterizations were conducted by nanoparticle tracking analysis, transmission electron microscopy (TEM), Western blotting, nanoflow cytometry analysis, and the TNF-α inhibition ratio of macrophage [after stimulated by lipopolysaccharide (LPS)]. RNA-seq and proteomic analysis with liquid chromatography tandem mass spectrometry (LC–MS/MS) were used to inspect the lot-to-lot consistency of the EV products. Repeated toxicity was evaluated in rats after administration using trace liquid endotracheal nebulizers for 28 days, and respiratory toxicity was evaluated 24 h after the first administration. In vivo therapeutic effects were assessed in an LPS-induced ALI/ acute respiratory distress syndrome (ARDS) rat model. Results The quality criteria have been standardized. In a stability study, haMSC-EVs were found to remain stable after 6 months of storage at − 80°C, 3 months at − 20 °C, and 6 h at room temperature. The microRNA profile and proteome of haMSC-EVs demonstrated suitable lot-to-lot consistency, further suggesting the stability of the production processes. Intratracheally administered 1.5 × 108 particles/rat/day for four weeks elicited no significant toxicity in rats. In LPS-induced ALI/ARDS model rats, intratracheally administered haMSC-EVs alleviated lung injury, possibly by reducing the serum level of inflammatory factors. Conclusion haMSC-EVs, as an off-shelf drug, have suitable stability and lot-to-lot consistency. Intratracheally administered haMSC-EVs demonstrated excellent safety at the tested dosages in systematic preclinical toxicity studies. Intratracheally administered haMSC-EVs improved the lung function and exerted anti-inflammatory effects on LPS-induced ALI/ARDS model rats.

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Mesenchymal Stem Cells in Radiation-Induced Pulmonary Fibrosis: Future Prospects

Chen

Liu

Tong

2022

Cells

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Radiation-induced pulmonary fibrosis (RIPF) is a general and fatal side effect of radiotherapy, while the pathogenesis has not been entirely understood yet. By now, there is still no effective clinical intervention available for treatment of RIPF. Recent studies revealed mesenchymal stromal cells (MSCs) as a promising therapy treatment due to their homing and differentiation ability, paracrine effects, immunomodulatory effects, and MSCs-derived exosomes. Nevertheless, problems and challenges in applying MSCs still need to be taken seriously. Herein, we reviewed the mechanisms and challenges in the applications of MSCs in treating RIPF.

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Advances in mesenchymal stromal cell therapy for acute lung injury/acute respiratory distress syndrome

Cited by 3 publications

References 212 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

Manufacturing, quality control, and GLP-grade preclinical study of nebulized allogenic adipose mesenchymal stromal cells-derived extracellular vesicles

Mesenchymal Stem Cells in Radiation-Induced Pulmonary Fibrosis: Future Prospects

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