Myofibroblasts reduce angiogenesis and vasculogenesis in a vascularized microphysiological model of lung fibrosis
Cambria, E.; Blazeski, A.; Ko, E. C.; Thai, T.; Dantes, S.; Barbie, D. A.; Shelton, S. E.; Kamm, R. D.
Show abstract
Lung fibrosis, characterized by chronic and progressive scarring, has no cure. Hallmarks are the accumulation of myofibroblasts and extracellular matrix, as well as vascular remodeling. The crosstalk between myofibroblasts and vasculature is poorly understood, with conflicting reports on whether angiogenesis and vessel density are increased or decreased in lung fibrosis. We developed a microphysiological system that recapitulates the pathophysiology of lung fibrosis and disentangles myofibroblast-vascular interactions. Lung myofibroblasts maintained their phenotype in 3D without exogenous TGF-{beta} and displayed anti-angiogenic and anti-vasculogenic activities when cultured with endothelial cells in a microfluidic device. These effects, including decreased endothelial sprouting, altered vascular morphology, and increased vascular permeability, were mediated by increased TGF-{beta}1 and reduced VEGF secretion. Pharmacological interventions targeting these cytokines restored vascular morphology and permeability, demonstrating the potential of this model to screen anti-fibrotic drugs. This system provides insights into myofibroblast-vascular crosstalk in lung fibrosis and offers a platform for therapeutic development.
Matching journals
The top 10 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Soluble ECM promotes organotypic formation in lung alveolar model 95%
- Engineering microvascular networks using a KLF2 reporter to probe flow-dependent endothelial cell function 95%
- Patient-Specific Vascularized Tumor Model: Blocking TAM Recruitment with Multispecific Antibodies Targeting CCR2 and CSF-1R 95%
Similar papers in this journal
- Stochastic to Deterministic: A straightforward approach to create serially perfusable multiscale capillary beds 96%
- Female fibroblast activation is estrogen-mediated in sex-specific 3D-bioprinted pulmonary artery adventitia models 94%
- EDA Fibronectin Microarchitecture and YAP Translocation During Wound Closure 93%
Similar papers in this journal
- 3D bioprinting of an implantable xeno-free vascularized human skin graft 94%
- Dissolved gases from pressure changes in the lungs elicit an immune response in human peripheral blood 92%
- Similar but distinct: the impact of biomechanical forces and culture age on the production, cargo loading, and biological efficacy of human megakaryocytic extracellular vesicles for applications in cell and gene therapies 91%
Similar papers in this journal
- Multicompartmentalized microvascularized tumor-on-a-chip to study tumor-stroma interactions and drug resistance in ovarian cancer 93%
- Formins and Arp2/3 Reciprocally Regulate Contact Guidance on Aligned Collagen Fibrils 91%
- Empowering High Throughput Screening of 3D Models: Automated Dispensing of Cervical and Endometrial Cancer Cells 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.