a ventricle that beats and pumps lab-grown blood

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the cardiovascular diseases (CVD) are the leading cause of death worldwide. An estimated 17.9 million people died from cardiovascular disease in 2019, accounting for 32% of all deaths worldwide. This is why this area of ​​research is booming, especially the sub-area of artificial organs. Canadian researchers have recently developed a miniature model of a working heart ventricle. Made with real living heart cells, it beats hard enough to pump fluid through a tube. It will be used to study heart disease and test potential new therapies that do not require invasive surgery.

With almost 18 million deaths per year, cardiovascular diseases are a public health problem. The WHO describes them as a real burden. Fortunately, most cardiovascular disease can be prevented by addressing behavioral risk factors, such as smoking, poor diet and obesity, physical inactivity, and harmful use of alcohol.

It is important to detect cardiovascular diseases as soon as possible in order to start management with advice and medication. But sometimes surgical operations are necessary, particularly for heart valve repair and/or replacement or heart transplantation (donor or artificial organ).

Despite current engineering efforts organ on chip To build miniature heart models, some physiological aspects of the heart are often missing, including fiber orientation. Recently, researchers at the University of Toronto, led by Professor Milica Radisic, developed a small-scale model of a human left heart ventricle in the laboratory, roughly the size of a ventricle after 19 weeks’ gestation. The bioartificial tissue construct is made from living heart cells and beats hard enough to pump fluid inside a bioreactor, just like the real ventricle. The system is described in detail in the review. advanced biology.

Heart tissue larger than life

Many of the challenges facing tissue engineers are related to geometry. Although it is easy to grow two-dimensional human cells in a Petri dish, the results bear little resemblance to actual tissues or organs. live, especially everything related to fluid mechanics. Thus, the research team used an approach based on microfabricated elastomers (scaffolding) that allows the hierarchical assembly of sheets composed of cells aligned in 2D, in a functional conical cardiac ventricle.

It should be noted that scaffolds, adorned with grooves or mesh-like structures, are usually seeded with cardiac muscle cells and cultured in liquid medium. Over time, the cells grow together, forming tissue. The underlying shape or pattern of the scaffold causes the cells to take on a particular configuration. Electrical impulses are used to control the rate at which they beat.

Here, the researchers used three trapezoidal-shaped sheets with three different mesh orientations, ranging from -60° to +60°. They were seeded with cells derived from cardiovascular tissues of young rats. The operation was repeated twice to obtain three layers with three sheets. After a week in culture, to make this set of three flat layers look like a ventricle, they wrapped them around a tapered shaft, nicknamed a “mandrel.”

Screenshots from the university’s press release video. On the left (A), a layer of three sheets with three different mesh orientations. On the right (B), the winding process on the mandrel. © University of Toronto (modified by Laurie Henry for Trust My Science)

Finally, the team obtained a model of a cone-shaped left ventricle modeled on the size of a 19-week-old human left ventricle, with an inner diameter of 0.5 millimeters and a height of about 1 millimeter. the heart cells in 3D constructs it showed high viability in all 3 layers, after 7 days in culture.

In addition, the three overlapping layers of heart cells beat in unison, thanks to a series of small electrical discharges, and are capable of pumping fluid. Professor Milica Radisic states in a release : « So far, there have only been a handful of attempts to create a true 3D model of a ventricle, rather than flat sheets of heart tissue. Virtually all of them were made from a single layer of cells. But a real heart has many layers, and the cells in each layer are oriented at different angles. When the heart beats, these layers not only contract, but also twist, like twisting a towel to squeeze out water. This allows the heart to pump more blood than it would otherwise. ».

The hope of leading to new therapies

This new model could offer researchers a new way to study a wide range of heart diseases and conditions, as well as test potential therapies. Professor Milica Radisic says: “ With these models, we can study not only cell function, but also tissue function and organ function, all without the need for invasive surgery or animal experimentation. We can also use them to screen large libraries of drug candidate molecules and estimate their positive or negative effects. ».

Indeed, in the human heart, the left ventricle is the one that pumps newly oxygenated blood to the aorta, and from there to the rest of the body. Sargol Okhovatian (BME PhD student) explains: “ With our model, we can measure stroke volume (the amount of fluid ejected each time the ventricle contracts) as well as the pressure of that fluid. Both were almost impossible to obtain with previous models. ».

Thus, the authors measured stroke volume and pressure using a conductance catheter, the same tool used to assess these parameters in patients. Currently, the model can only produce a small fraction, less than 5%, of the ejection pressure compared to a real heart, which is normal given the scale of the model. In fact, it contains only three layers. To simulate heart muscle more realistically, 11 would be needed, increasing ejection volume and pressure.

However, as the number of layers increases, the intermediate layers no longer have access to oxygen and begin to die, requiring further research on the vascularization of the model. Finally, in addition to the issue of vascularization, the authors note that future work should focus on increasing cell density to increase ejection volume and pressure. It will also be necessary to find a way to shrink or possibly remove the scaffolding.

Although the concept represents significant progress, there is still a long way to go before such fully functional artificial organs are available. Meanwhile, known behavioral risk factors for cardiovascular disease, such as poor diet, physical inactivityyou of smoking and harmful use of the alcohol. These prevention and awareness plans promoted by the WHO make it possible to avoid complications that require major surgical interventions.

Font : advanced biology

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