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Journal article
A micro-lung chip with macrophages for targeted anti-fibrotic therapy
Biofabrication, v 17(2), p25020
01 Apr 2025
PMID: 39914008
Featured in Collection : Research Supported by Drexel Libraries' OA Programs
Abstract
Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease of unknown etiology. Macrophages are implicated in the fibrotic process, but exhibit remarkable plasticity in the activated immune environment in vivo, presenting significant challenges as therapeutic targets. To explore the influence of macrophages on IPF and develop macrophage-targeted therapies, we engineered a micro-lung chip with a lung epithelium-interstitium tissue unit to establish a controlled immune environment containing only macrophages. We discovered that macrophages exacerbated inflammation and fibrosis by comparing microchips treated with bleomycin (BLM) in the presence and absence of macrophages. Based on the duration of BLM treatment, we established pathological models corresponding to inflammation and fibrosis stages. Transcriptome analysis revealed that activation of the PI3K-AKT signalling pathway facilitates the transition from inflammation to fibrosis. However, LY294002, a PI3K inhibitor, not only suppressed fibrosis and decreased the accumulation of M2 macrophages but also intensified the severity of inflammation. These findings suggest that macrophages play a pivotal role in the potential development at the tissue level. The micro-lung chip co-cultured with macrophages holds significant potential for exploring the pathological progression of IPF and elucidating the mechanisms of anti-fibrotic drugs.
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Details
- Title
- A micro-lung chip with macrophages for targeted anti-fibrotic therapy
- Creators
- Jingjing Xia - Tsinghua Univ, Dept Mech Engn, Beijing 100084, Peoples R ChinaRuming Dong - China Medical UniversityYongcong Fang - Tsinghua Univ, Dept Mech Engn, Beijing 100084, Peoples R ChinaJiabin Guo - China Medical UniversityZhuo Xiong - Tsinghua Univ, Dept Mech Engn, Beijing 100084, Peoples R ChinaTing Zhang - Tsinghua UniversityWei Sun (Corresponding Author) - Drexel University, Mechanical Engineering and Mechanics
- Publication Details
- Biofabrication, v 17(2), p25020
- Publisher
- Institute of Physics
- Number of pages
- 13
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Mechanical Engineering and Mechanics
- Web of Science ID
- WOS:001431399200001
- Scopus ID
- 2-s2.0-85218944985
- Other Identifier
- 991022040873304721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Engineering, Biomedical
- Materials Science, Biomaterials