New Pulmonary Fibrosis Study Finds Humanized Mouse Model

Researchers at Preclina Inc. in Seoul, South Korea, have published a study on a new humanized mouse model for pulmonary fibrosis, a progressive lung disease characterized by excessive extracellular matrix deposition. According to the study, conventional preclinical models are unsuitable for evaluating human-specific antibody and cell therapies due to their inability to replicate the complexity of the human immune environment. The researchers developed two humanized mouse models with functional human immune components, one engrafted with peripheral blood mononuclear cells (PBMCs) and the other with hematopoietic stem cells (HSCs). The study found that the HSC-humanized model demonstrated stable multilineage engraftment and consistent fibrotic pathology, making it a clinically relevant platform for investigating human immune responses in IPF and for preclinical evaluation of human-targeted therapies.

Key Takeaways:

• Conventional preclinical models, such as the bleomycin (BLM)-induced lung fibrosis (BILF) model, are unsuitable for evaluating human-specific antibody and cell therapies.
• Two humanized mouse models with functional human immune components were developed, one engrafted with PBMCs and the other with HSCs.
• The HSC-humanized model demonstrated stable multilineage engraftment, absence of graft-versus-host disease (GvHD), and consistent fibrotic pathology.
• Nintedanib treatment significantly ameliorated fibrotic changes in both models.
• The HSC-humanized BILF model is a clinically relevant platform for investigating human immune responses in IPF and for preclinical evaluation of human-targeted therapies.
• Additional research is needed to fully understand the mechanisms of pulmonary fibrosis and to develop effective therapies.

Statistics:

• 79.9% ± 9.7% of CD45 cells comprised human T cells in the PBMC-humanized model.
• 56.8% ± 25.4% of cells in the HSC-humanized model were B cells.
• 20.1% ± 28.3% of cells in the HSC-humanized model were T cells.
• Nintedanib treatment significantly reduced fibrotic changes in both models.

Sources:

• Establishment of a humanized mouse model of pulmonary fibrosis for advancing drug validation strategies. Scientific Reports, 2025;15(1):34748.
• NewsRx. New Pulmonary Fibrosis Study Findings Have Been Reported by Yuri Chae and Colleagues (Establishment of a humanized mouse model of pulmonary fibrosis for advancing drug validation strategies). Respiratory Therapeutics Week. October 20, 2025; p 3586.