Hydrogel-Embedded Precision-Cut Lung Slices Recapitulate Fibrotic Gene Expression and Enable Therapeutic Response...

Area of Science:

• Biomedical Engineering
• Pulmonary Medicine
• Drug Discovery

Background:

• Precision-cut lung slices (PCLS) are valuable for studying lung tissue interactions and pre-clinical drug studies.
• Current ex vivo models for pulmonary fibrosis have short timelines due to cell viability issues, limiting chronic disease mechanism studies.

Purpose of the Study:

• To develop an improved ex vivo model for pulmonary fibrosis by embedding PCLS in engineered hydrogels.
• To extend the culture duration and enhance the study of chronic fibrotic processes.

Main Methods:

• PCLS were embedded in engineered hydrogels and exposed to pro-fibrotic cues.
• Cell viability was assessed over 3 weeks.
• Gene expression patterns were analyzed.
• The efficacy of Nintedanib treatment was evaluated.

Main Results:

• Hydrogel-embedded PCLS maintained over 80% cell viability for 3 weeks.
• Gene expression profiles in the model resembled those in human fibrotic lung tissue.
• Nintedanib treatment showed moderate reduction in fibroblast activation and influenced epithelial cell differentiation.

Conclusions:

• Hydrogel embedding significantly extends the viability of PCLS for ex vivo studies.
• This enhanced PCLS model provides a more robust platform for investigating pulmonary fibrosis mechanisms and evaluating therapeutic interventions.
• The model offers a novel approach for studying lung diseases and treatments using human tissues.