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High-throughput 3D microvessel-on-a-chip model to study defective angiogenesis in systemic sclerosis
Bart Kramer1, Claudio Corallo2,3, Angelique van den Heuvel4
1Mimetas BV, Leiden, The Netherlands. b.kramer@mimetas.com.
Scientific Reports
|October 8, 2022
Summary
Researchers developed an angiogenesis-on-a-chip model to study systemic sclerosis (SSc) vasculopathy. The model successfully mimicked SSc microvascular damage and showed potential for testing drugs to protect against vessel regression.
Area of Science:
- Biomedical Engineering
- Vascular Biology
- Regenerative Medicine
Background:
- Systemic sclerosis (SSc) is characterized by early vascular impairment, with endothelial to mesenchymal transition (EndoMT) implicated in endothelial cell damage.
- Current models lack the physiological relevance to accurately study SSc-related vasculopathies and test therapeutic interventions.
Purpose of the Study:
- To develop an advanced angiogenesis-on-a-chip platform for studying SSc and other vasculopathies.
- To assess the platform's suitability for evaluating disease parameters and testing potential drug compounds.
Main Methods:
- Developed a 3D microvessel model using human serum instead of Fetal Bovine Serum (FBS).
- Exposed the model to pro-inflammatory (TNFα) and pro-fibrotic (TGFβ) cytokines to induce vasculopathy.
- Tested the efficacy of TGFβ-ALK5 inhibition and TNFα neutralization in preventing microvascular damage.
- Utilized sera from SSc patients to evaluate the model's translatability.
Main Results:
- The 3D microvessel model demonstrated structural alterations and destructive vasculopathy (loss of small vessels) upon exposure to TNFα and TGFβ.
- Inhibition of TGFβ-ALK5 signaling or TNFα neutralization effectively protected microvessels from cytokine-induced damage.
- Sera from SSc patients exhibited anti-angiogenic effects on the 3D vessel model, confirming its clinical relevance.
Conclusions:
- The developed angiogenesis-on-a-chip platform accurately mimics SSc-related microvascular dysfunction.
- The model is a valuable tool for compound testing and identifying drugs to prevent or treat microvascular destabilization in SSc.
- This platform facilitates personalized drug treatment strategies for SSc patients by enabling direct translatability.
