Simulator for heart cells
Heart muscle cells need physical activity even when cultivated outside the body. Researchers at the University of Toronto, working under the guidance of Professor Milica Radisic, have developed a device that applies a strict training protocol to growing small fragments of heart tissue and evaluating the strength of contractions of its cells. This platform, which is an ideal tool for testing the effects of potential drugs, can bring the introduction of personalized medicine methods into clinical practice closer.
According to Radizik, many potential new drugs do not reach the clinic because of their toxicity, and toxicity to heart tissue is a very serious problem. Such drugs can be tested on heart cells grown in the laboratory, but these cells even look different from the cells of a living heart and do not provide reliable information.
The authors have created a device that allows cells and tissues cultivated in the laboratory to form three-dimensional structures resembling the structures of the human body. Five years ago, they developed the Biowire platform, in which heart cells grow around a silk thread. When an electric charge is passed through, the cells inside such a device lengthen and acquire signs of adult cardiomyocytes.
As part of their latest work, Radizik and her colleagues presented the new Biowire II platform. It provides the cultivation of cardiac muscle cells in the gap between two parallel strands of elastic polymer located at a distance of 3 millimeters from each other. With each contraction, the cells forming the muscle strip stretch the threads. Measuring the degree of bending of threads allows researchers to determine the strength of contraction in real time.
The advantage of this system is that it allows you to determine the effect of each specific compound on the functional state of the heart by analyzing the strength of contraction and other key functional indicators. With its help, specialists can determine whether a particular molecule weakens or enhances cardiac activity, identifying potential drugs for the treatment of heart diseases, as well as identifying drugs for the treatment of other diseases that have side effects on heart tissue.
As in the original version of Biowire, electrical impulses are used to stimulate contractions and "train" heart cells. The authors claim that they have managed to improve the training protocol in such a way that in just 6 weeks a fragment of heart tissue is formed in the device that is close to reality.
As part of their work, they created not only fragments of ventricular and atrial tissue, but also fragments of heteropolar tissue having ventricular and atrial sections. Such complex structures allow us to study the effect of drugs that selectively affect the functions of different parts of the heart.
The authors note that the most impressive results were obtained when the devices were populated with six different cell lines. Three of them were grown from cells of patients with left ventricular hypertrophy, while the remaining three were grown from cells of people who do not suffer from this disease.
It was a "blind" experiment, none of the researchers who conducted it knew who the cells belonged to. However, as they grew in the device, the tissue from the cells of patients with left ventricular hypertrophy was unmistakably determined by weak contractility, which is one of the main signs of the disease.
The ability to accurately reproduce the manifestations of heart disease opens up new opportunities for personalized medicine. In addition to studying the progression of a particular patient's disease, a heart tissue model can be used to screen several potential treatments simultaneously. This, by way of exclusion, will eventually allow us to determine the most effective therapeutic approach.
While such an application is still far away, the Biowire II platform has already found its application in a commercial company testing cardiac preparations for pharmaceutical companies on laboratory-grown cultures of cardiac tissue.
Article by Yimu Zhao et al. A Platform for Generation of Chamber-Specific Cardiac Tissues and Disease Modeling is published in the journal Cell.
Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the University of Toronto: U of T Engineering researchers design 'training gym' for lab-grown heart cells.