With every heartbeat comes a rhythmic pulse that helps blood flow through the body. Understanding this pulsatile flow can offer insights on the impacts of blood vessel development and cardiovascular disease.
In a recent study published in the Lab on a Chip journal, researchers at the Morgridge Institute developed an “organ-on-a-chip” model to study pulsatile flow in a more biologically relevant way.
Using stem-cell derived cardiomyocytes, the team created cardiac spheroids – small clusters of cells about 100 to 300 microns in diameter – that more accurately represent the biological function of a full tissue or organ.
“We are able to generate pulsatile flow from a real heart contraction,” says Tongcheng Qian, assistant scientist in the Skala Lab and first author of the study. “Compared to previous methods, it’s kind of unique.”
Qian says that other models generate pulsatile flow with arbitrary frequencies generated by a computer. But these systems are often static, and typically have pre-calculated frequency and magnitude.
“In reality, your heart contraction always changes,” Qian says.
The unique approach combined imaging of the spheroids to measure contraction, with a pressure pump to generate pulsatile flow through a fluid microchannel lined with endothelial cells.
To measure the flow, they imaged small fluorescent beads flowing through the channel over time, which also provided a real-time feedback loop to drive the pressure pump.
The blood vessels that make up the circulatory system are lined with endothelial cells that serve as a barrier to protect the microenvironment of blood, so maintaining the integrity of endothelial cells is important.
Babies with heart defects and irregular blood flow in utero can have issues with endothelial cells, says Morgridge Investigator Melissa Skala. She says this study is a good proof of concept to demonstrate the mechanical force that drives the development of these cells.
Qian and his team tested different pulsatile flows by applying drug treatments that altered the contraction of the “heart-on-a-chip” spheroids, which then affected the development of endothelial cells downstream.
“It then sets the stage to test other drugs that could be used to correct abnormal flows,” Skala adds, “And see how those drugs then affect endothelial cells as well.”
In addition to endothelial cell development, Qian sees this system as a way to study the complexity of the whole cardiovascular system.
In addition to shuttling oxygen to other tissues and organs, blood is also comprised of cells and proteins that impact the endocrine system and the immune system – and their function is also dependent on pulsatile flow.
Skala adds that the system could also be applied to mature endothelial cells, to look at how they are affected in someone with a chronic heart condition.
It isn’t easy to accurately capture the complex biomechanical microenvironment of the ever-changing bloodstream – but this new system is a good step forward.
Adds Skala: “It required some image processing, it required real time feedback, it required accuracy and precision…this is a fun project.”