Human umbilical cord-derived mesenchymal stem cells thwart pyroptosis of lung tissue cells in septic mice

doi:10.12307/2025.547

Abstract

Abstract: BACKGROUND: Acute lung injury is a common severe complication in sepsis patients, with a complex pathogenesis, for which there is currently no effective pharmacological treatment. The therapeutic mechanism by which human umbilical cord-derived mesenchymal stem cells improve sepsis-induced acute lung injury through the inhibition of excessive cellular pyroptosis is increasingly receiving attention.
OBJECTIVE: To investigate the effects and mechanisms of human umbilical cord-derived mesenchymal stem cells on cellular pyroptosis in lung tissues of mice with sepsis-induced acute lung injury.
METHODS: Totally 48 male Balb/c mice were randomly divided into sham, model, and treatment groups (n=16 per group). The model and treatment groups underwent cecum ligation and puncture to establish a sepsis-induced acute lung injury model, while the sham group underwent laparotomy without further procedures. The treatment group received a tail vein injection of 200 μL of human umbilical cord-derived mesenchymal stem cell suspension (5×105 cells) 6 hours after the procedure, while the model and sham groups received 200 μL of saline 6 hours after the surgery. Twenty-eight hours post-procedure, five mice from each group were randomly selected for tail vein injection of Evans blue dye to assess pulmonary vascular permeability. The remaining mice from each group had their bronchoalveolar lavage fluid and lung tissues collected for ELISA to measure levels of interleukin-1β and interleukin-18, cell counts, and macrophage numbers in the bronchoalveolar lavage fluid. Hematoxylin and eosin staining was used to observe the pathological morphology of lung tissue. TUNEL staining was used to assess cellular pyroptosis. RT-PCR and western blot analyses were conducted to measure mRNA and protein expression levels of Toll-like receptor 4, GSDMD, and Caspase-11 in lung tissues.
RESULTS AND CONCLUSION: Compared to the model group, the treatment group showed a significant decrease in pulmonary vascular permeability at 28 hours post-procedure (P < 0.05), reduced levels of interleukin-1β and interleukin-18 in bronchoalveolar lavage fluid (P < 0.05), and lower cell and macrophage counts (P < 0.05). Lung injury severity was reduced, with a decreased pyroptosis index (P < 0.05) and significantly lower levels of Toll-like receptor 4, GSDMD, GSDMD-N, and Caspase-11 mRNA and protein expression in lung tissues (P < 0.05). These results suggest that human umbilical cord-derived mesenchymal stem cells may improve the severity of sepsis-induced lung injury to some extent by inhibiting the activation of the Toll-like receptor 4/Caspase-11/GSDMD signaling pathway and reducing cellular pyroptosis in lung tissues.

Key words: human umbilical cord-derived mesenchymal stem cell, Toll-like receptor 4, Caspase-11, GSDMD, acute lung injury, acute respiratory distress syndrome, pyroptosis, sepsis, engineered stem cell

CLC Number:

He Changliang, Wang Yan, Luo Ling, Liu Jian. Human umbilical cord-derived mesenchymal stem cells thwart pyroptosis of lung tissue cells in septic mice[J]. Chinese Journal of Tissue Engineering Research, 2025, 29(31): 6642-6648.

Figures/Tables 2

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