Understanding the interactions between endothelial cells and vascular smooth muscle cells is critical for the study of vascular disease. Yet, there are few existing models which can simply and reliably recapitulate the cellular crosstalk in human microvascular networks.
However, in a recent publication (see Reference 1), researchers from Leiden University Medical Center in the Netherlands demonstrated just such a model for human blood vessel function using organ-on-a-chip technology from AIM Biotech.
Creating a human vascular network on a chip
The authors combined the key human blood vessel cell types of endothelial cells (EC) and mural cells—consisting of vascular smooth muscle cells (VSMC) and vascular pericytes—to create a functional
vascular system on AIM Biotech 3D cell culture chips. Specifically, the group used human induced pluripotent stem cells to generate induced ECs and induced VSMCs. They also utilized the primary cell types of human brain VSMCs and human brain vascular pericytes. Finally, the ECs were combined with one of the mural cell types within the central chamber of an AIM chip. Just seven days later, the self-assembled and intact vascular networks were present in the entire central chamber of the chip.
Assaying functionality of the human vascular network
The authors demonstrated that the formed microvascular network had a continuous lumen and that the cells were functional. They added fluorescent beads or fluorescent liquid compound (dextran) on the side channels of the AIM chip. In this video (left), you can see how the beads (upper panels) or the dextran (lower panels) flow inside the lumen of the vessels.
In addition, they demonstrated that the vascular cells attached to the vessels were functional using a calcium assay. Take a look at the second video (left, below) to see how the cells activate after media refreshment or stimulation with endothelin-I, ensuring functionality.
Human vascular disease model in AIM Biotech 3D cell culture chips
Having shown that these human vascular networks are functional, the authors further demonstrated their utility as a realistic model for human vascular disease. They added to the AIM chip a molecule that disrupts the crosstalk between the endothelial and vascular smooth muscle cells—a main cause of vascular disease—and found that the vessel integrity was disrupted. This response demonstrates the functional integrity of the resulting human vascular networks created in AIM chips, indicating the model as appropriate for representing human vascular function and disease states.
The authors assert that the described model will be useful to study and quantify changes in vascular architecture and function during vascular
development or upon drug treatment. And clinically, this may translate into a better understanding of vascular disease conditions and predicting drug efficiency.
Beyond establishing the viability of this individual model, this study also demonstrated how the sophisticated architecture of AIM Biotech’s 3D cell culture systems, combined with its easy-to-use features, are critical for advancing in-vitro human organ models in spaces where traditional tools are lacking.
References
1. Engineered 3D vessel-on-chip using hiPSC-derived endothelial- and vascular smooth muscle cells. Villa Cuenca M, Cochrane A, van den Hill FE, …, Lesnik Oberstein SAJ, Mummery CL, Orlova VV. Stem Cell Reports 2021. DOI:https://doi.org/10.1016/j.stemcr.2021.08.003
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