Fibrosis and Microvasculature on a chip
A beautiful paper from Hasse lab at EMBL Barcelona modelling fibrosis in the lung and heart to study the implications of fibrosis on microvasculature. They used a macro-scale side-by-side channel chip, previously developed in the lab of Roger Kamm. The authors developed this vasculature on a chip to assess endothelial barrier function, vascular morphology, and matrix properties with (or without) human primary cardiac or lung fibroblasts.
Results
The results demonstrated that lung and cardiac microvascular tissues responded to fibrotic stimuli in differential manner. So that treatment with transforming growth factor-β (TGF-β) resulted in increased stiffness and alpha-smooth muscle actin (αSMA) expression in lung-like microenvironments. On the other hand, treatment with TGF-β resulted in tissue softening of cardiac microvessels and decrease in αSMA expression. TGF-β was also shown to have a severe negative impact on the endothelium without stromal cell support.
DigesTable of the paper Akinbote, A., et al. (2021). “Classical and non-classical fibrosis phenotypes are revealed by lung and cardiac like microvascular tissues on-chip.” Frontiers in Physiology 12: 735915. This paper is reproduced under https://creativecommons.org/licenses/by/4.0/. The image of the chip was edited for better clarity, data in the table and text were compiled and interpreted by AZAR Innovations.
Method
The human-induced pluripotent stem cell-derived endothelial cells and primary human cardiac and lung fibroblasts were encapsulated within a fibrin hydrogel in the central channel. The central channel was separated from empty side channels by micropillars.
Fabrication: molding with PDMS
Sterilization: UV treatment
Cells incorporation: cells with thrombin and fibrinogen solution were inserted to the gel channel
Perfusion/Refreshing: The media was refreshed daily and cultured under static conditions
Treatment: TGF-β
On-chip read-outs: on-chip monitoring, end-point microscopy
Off-chip read-outs: antibody microarray, off-chip imaging, immuno-histo chemistry, ELISA
Strong points:
+ Well-established protocol to co-culture fibroblasts and endothelial cells
+ hiPSC-derived endothelial cells in combination with primary human fibroblasts
+ Using fibrin that can be remodeled by the fibroblasts
Nothing is perfect! The system can also improve:
– PDMS, no indication of absorption of small molecules
– No flow during the formation of the micro-vasculature, daily medium refreshment
Conclusion and outlook
The results of this study can be used for future studies on the mechanisms behind distinct fibrotic phenotypes. This platform has the potential to examine anti-fibrotic therapies on patient-specific hiPSCs in the future.
Contact us if you want to know more about this system or similar technologies!
