Acute Lung Injury: Disease Modelling and the Therapeutic Potential of Stem Cells

Lian, Jiarong; Lin, Juntang; Zakaria, Norashikin; Yahaya, Badrul Hisham

doi:10.1007/5584_2020_538

Cited by 19 publications

(15 citation statements)

References 92 publications

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“…Intervention with ADMSCs reduced organ damage, as well as inflammatory infiltration and hemorrhage, in the lungs, and the diversity of the flora and the content of pathogenic bacteria in rats with sepsis increased significantly. According to the recommendations in the official document of the American Thoracic Society (ATS), at least three of four main characteristics of ALI should be present in the ALI animal model, including histological evidence of tissue injury, alteration of the alveolar capillary barrier, inflammatory response, and physiological dysfunction [75]. In our results, pulmonary H&E showed typical inflammatory infiltration in sepsis-associated ALI, and decreased plasma IL-6/TNF-α through MSCs treatment, effectively alleviated inflammatory infiltration, and reduced bleeding and edema.…”

Section: Discussionmentioning

confidence: 99%

Adipose-derived mesenchymal stem cells attenuate acute lung injury and improve the gut microbiota in septic rats

et al. 2020

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Background We hypothesized that adipose-derived mesenchymal stem cells (ADMSCs) may ameliorate sepsis-induced acute lung injury (ALI) and change microorganism populations in the gut microbiota, such as that of Firmicutes and Bacteroidetes. Methods A total of 60 male adult Sprague-Dawley (SD) rats were separated into three groups: the sham control (SC) group, the sepsis induced by cecal ligation and puncture (CLP) group, and the ADMSC treatment (CLP-ADMSCs) group, in which rats underwent the CLP procedure and then received 1 × 106 ADMSCs. Rats were sacrificed 24 h after the SC or CLP procedures. To study the role of ADMSCs during ALI caused by sepsis and examine the impact of ADMSCs on the gut microbiome composition, rat lungs were histologically evaluated using hematoxylin and eosin (H&E) staining, serum levels of pro-inflammatory factors were detected using enzyme-linked immunosorbent assay (ELISA), and fecal samples were collected and analyzed using 16S rDNA sequencing. Results The serum levels of inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-6, were significantly increased in rats after the CLP procedure, but were significantly decreased in rats treated with ADMSCs. Histological evaluation of the rat lungs yielded results consistent with the changes in IL-6 levels among all groups. Treatment with ADMSCs significantly increased the diversity of the gut microbiota in rats with sepsis. The principal coordinates analysis (PCoA) results showed that there was a significant difference between the gut microbiota of the CLP-ADMSCs group and that of the CLP group. In rats with sepsis, the proportion of Escherichia–Shigella (P = 0.01) related to lipopolysaccharide production increased, and the proportion of Akkermansia (P = 0.02) related to the regulation of intestinal mucosal thickness and the maintenance of intestinal barrier function decreased. These changes in the gut microbiota break the energy balance, aggravate inflammatory reactions, reduce intestinal barrier functions, and promote the translocation of intestinal bacteria. Intervention with ADMSCs increased the proportion of beneficial bacteria, reduced the proportion of harmful bacteria, and normalized the gut microbiota. Conclusions Therapeutically administered ADMSCs ameliorate CLP-induced ALI and improves gut microbiota, which provides a potential therapeutic mechanism for ADMSCs in the treatment of sepsis.

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Section: Discussionmentioning

confidence: 99%

Adipose-derived mesenchymal stem cells attenuate acute lung injury and improve the gut microbiota in septic rats

et al. 2020

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“…Acute lung injury (ALI) is a severe clinical condition with high morbidity and mortality that usually results in the development of multiple organ dysfunction (Lian et al, 2020). Previous research by Chen et al, (2010Chen et al, ( , 2012Chen et al, ( , 2015 found that endothelial ITGB4 has proinflammatory properties in ventilator-induced lung injury.…”

Section: Introductionmentioning

confidence: 99%

Airway epithelial integrin β4‐deficiency exacerbates lipopolysaccharide‐induced acute lung injury

Wang

Luo

et al. 2021

Journal Cellular Physiology

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Airway epithelial cells, the first barrier of the respiratory tract, play an indispensable role in innate immunity. Integrin β4 (ITGB4) is a structural adhesion molecule that is involved in the pathological progression of acute inflammatory diseases and is downregulated in asthmatic patients. Research has shown that endothelial ITGB4 has proinflammatory properties in acute lung injury (ALI). However, the role of epithelial ITGB4 in a murine ALI model is still unknown. This study investigated the role of ITGB4 in lipopolysaccharide (LPS)-induced ALI. We found that ITGB4 in the airway epithelium had remarkably increased after the introduction of LPS in vivo and in vitro. Then, we constructed airway epithelial cell-specific ITGB4 knockout (ITGB4 −/− ) mice to study its role in ALI. At a time point of 12 h after the tracheal injection of LPS, ITGB4 −/− mice showed increased macrophages (mainly M1-type macrophages) and neutrophil infiltration into the lungs; inflammation-related proteins including interleukin (IL)-6, tumor necrosis factor, and IL-17A were significantly elevated compared to their levels in ITGB4 +/+ mice. Furthermore, we investigated the role of ITGB4 in the anti-inflammatory response. Intriguingly, in the ITGB4 −/− + LPS group, we found significantly reduced expression of antiinflammatory factors, including IL-10 messenger RNA (mRNA) and ARG-1 mRNA.We also observed that monocyte chemotactic protein (MCP-1) increased significantly both in vivo and in vitro. Airway epithelium activates macrophages, most likely driven by MCP-1, which we confirmed in the coculture of epithelia and macrophages. These phenomena indicate that ITGB4 in airway epithelial cells plays an important role in the process of inflammation and activation of macrophages in ALI. Overall, these data demonstrated a novel link between airway epithelial ITGB4 and the inflammatory response in LPS-induced ALI.

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“…4 Transplanted cells need a period to be vascularized, nourished, oriented, or attracted into the location of tissue injury to start biological functions by inflammatory mediators/cells, nutrient factors from supporting cells, or direct interactions between cells. Clinical application of stem cells, recently started in patients with moderate-to-severe ARDS using low, intermediate, or high doses of MSCs, 5 demonstrated that patients could develop the tolerance against the intravenous infusion of allogeneic, bone marrow-derived human MSCs. Thus, there is an urgent need to further improve applications of MSCs in patients with ARDS.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of interactions between lung‐origin telocytes and mesenchymal stem cells to treat experimental acute lung injury

Zhang

Song

Shi

et al. 2020

Clinical & Translational Med

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Acute Lung Injury: Disease Modelling and the Therapeutic Potential of Stem Cells

Cited by 19 publications

References 92 publications

Adipose-derived mesenchymal stem cells attenuate acute lung injury and improve the gut microbiota in septic rats

Adipose-derived mesenchymal stem cells attenuate acute lung injury and improve the gut microbiota in septic rats

Airway epithelial integrin β4‐deficiency exacerbates lipopolysaccharide‐induced acute lung injury

Mechanisms of interactions between lung‐origin telocytes and mesenchymal stem cells to treat experimental acute lung injury

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