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The following is a summary of “Biochemical and transcriptomic evaluation of a 3D lung organoid platform for pre-clinical testing of active substances targeting senescence,” published in the January 2024 issue of Pulmonology by Brand et al.
Chronic lung diseases, including chronic obstructive pulmonary disease and cystic fibrosis, pose significant challenges due to their incurable nature. Epithelial senescence, characterized by dysfunctional cell cycle arrest, plays a pivotal role in driving the progression of these debilitating conditions. Thus, targeting lung epithelial cells presents a promising avenue for therapeutic intervention.
In this study, researchers introduce a novel 3D airway lung organoid platform designed for preclinical assessment of active substances targeting senescence, toxicity, and inflammation in a standardized manner, utilizing a 96-well format. Senescence induction was achieved through doxorubicin treatment, with senescence-associated galactosidase activity as a quantifiable marker. Notably, pharmaceutical compounds such as quercetin demonstrated the ability to counteract doxorubicin-induced senescence while preserving organoid integrity. Leveraging single-cell sequencing techniques, they identified a distinct subset of cells expressing senescence markers, the abundance of which was mitigated by quercetin administration. Furthermore, doxorubicin triggered the upregulation of detoxification factors primarily in goblet cells, an effect observed independently of quercetin treatment.
In summary, the innovative platform facilitates the comprehensive analysis of senescence-related processes, offering a robust tool for the preclinical evaluation of various compounds, including natural products. By providing a high-throughput screening platform, this approach holds promise for reducing reliance on animal testing and expediting the identification of potential therapeutics for chronic lung diseases.
Source: respiratory-research.biomedcentral.com/articles/10.1186/s12931-023-02636-7