Daily Ards Research Analysis

BACKGROUND: Human umbilical cord mesenchymal stem cells (hUC-MSCs) show potential for treating acute respiratory distress syndrome (ARDS), however, their homing to the lungs and survival time are insufficient. In this study, we evaluated whether pulsed focus ultrasound (pFUS) could promote the homing and prolonged retention of hUC-MSCs in the lungs of ARDS mice and explored the mechanisms involved. METHODS: Mice were divided into four groups: the NC group, the LPS group, the MSCs group, and the pFUS + MSCs group. Except for the NC group, the other three groups were constructed as ARDS models and given PBS, MSCs and pFUS + MSCs interventions. hUC-MSCs were used to assess lung tissue injury by HE staining, inflammatory cell count in alveolar lavage fluid (BALF), and expression of Tnf, Il1b and Il6 in the lung tissues; and apoptosis and proliferation in the lung tissues were assessed by TUNEL and immunofluorescence. Bioluminescence imaging was used to detect the homing rate and survival of hUC-MSCs in mouse lungs from 1 to 7 days. Cxcl5 and Igf1 was found to be differentially expressed and highly enriched by mRNA sequencing in MSC and sonicated groups and verified by PCR combined with ELISA. RESULTS: Compared with the LPS group, the lung inflammatory infiltrate and lung tissue damage in the MSCs group and pFUS + MSC group were alleviated, the number of inflammatory cells in the BALF and the expression of Tnf, Il1b and Il6 in the lung tissues were reduced, the expression of TUNEL-positive cells was reduced, and the expression of PCNA-positive cells was increased, and the decrease or increase was more significant in the pFUS + MSC group (P < 0.05). pFUS increased the number of hUC-MSCs homing in the lungs and prolonged lung survival to day 6 and significantly up-regulated lung tissue levels of SDF-1, ICAM-1, CXCL5 and IGF-1 compared to the MSCs group (P < 0.05). CONCLUSIONS: pFUS preconditioning may improve lung homing and prolong survival of hUC-MSCs by upregulating the levels of homing-associated factors SDF-1, ICAM-1, CXCL5 and IGF-1, which in turn improves ARDS.

CONTEXT: Direct preclinical lipopolysaccharide acute lung injury (ALI) models are commonly used to study acute respiratory distress syndrome. Differences in lipopolysaccharide delivery methods may impact lung injury severity and reproducibility. HYPOTHESIS: We hypothesized that the severity and variability of ALI outcomes in mice would differ depending on the technique of lipopolysaccharide administration. METHODS AND MODELS: Male and female C57BL/6 mice were administered lipopolysaccharide (2.25 mg/kg) via four methods: 1) intratracheal intubation; 2) intranasal; 3) surgical transtracheal by either needle puncture; or 4) by catheter. ALI severity and variability were assessed at 72 hours post-lipopolysaccharide via histological scoring and bronchoalveolar lavage fluid (BALF) analysis (total protein, cell counts, interleukin-6 [IL-6]). The relative distribution of Evans Blue dye was also assessed for each model (lungs vs. stomach). RESULTS: Distinct lung injury patterns were observed between the four methods. The transtracheal with catheter method demonstrated significantly greater lung injury scores than the intratracheal intubation and intranasal techniques. Both transtracheal methods produced greater alveolar neutrophil counts, increased proteinaceous debris, fewer hyaline membranes, and lower variability than non-surgical techniques. The transtracheal with catheter method produced higher BALF total cell counts and IL-6 levels than intratracheal intubation. Transtracheal methods also resulted in more localized Evans Blue dye distribution in the lungs. Male mice exhibited more severe lung injury scores and higher BALF protein concentrations than females. INTERPRETATION AND CONCLUSIONS: This study demonstrates that the choice of technique to administer lipopolysaccharide impacts injury severity, phenotype, and variability. The surgical transtracheal with catheter technique produced the most robust and least variable ALI phenotype; however, this technique is associated with increased procedural complexity. Our results will allow researchers to tailor their model choice to align with their specific study objectives.

Acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis are major respiratory conditions associated with significant morbidity and, in some cases, high mortality. A variety of animals models have been established to study these disorders, primarily focusing on histologic alterations, cellular signalling pathways, inflammatory responses, lung perfusion, gas-exchange abnormalities, and response to emerging therapies. Imaging techniques play a crucial role in these investigations, enabling in vivo assessment of lung structure and function. The most widely used imaging modalities include computed tomography (CT), positron emission tomography (PET), and electrical impedance tomography (EIT). While CT and, to a variable extent, PET involve ionizing radiation, EIT is a radiation-free technique. Despite anatomical differences between species, many imaging and physiological findings observed in animal models are consistent with those seen in critically ill patients, enhancing their translational relevance. This narrative review provides a comprehensive overview of the applicability of these imaging techniques in animal models and explores their relevance to human pathophysiology and clinical management.