Release date: 2016-09-07
Cell models derived from stem cells play an increasingly important role in the study of cardiac dysfunction. Researchers at the Technical University of Munich (TUM) have successfully produced cells that help to study the characteristics of the heart. The use of a luminescent molecular sensor not only makes the electrical activity of the cell visible, it also makes it possible to perform cell type identification for the first time.
In the past decade, so-called induced pluripotent stem cells have been produced in the laboratory. These stem cells are derived from white blood cells, for example, can be replicated indefinitely in the laboratory and become all possible types of cells. For example, heart cells produced in this way make it useful for investigating heart rhythm disorders. Animal applications in this application are not readily available for tissue samples from the patient's heart. However, cultured heart cells provide an opportunity to study such diseases in a "microcosm" manner.
“Our research solves several problems with the use of such cell models,†said Daniel Sinnecker, MD, PhD, of the University of Munich's Department of Cardiology at KLINIKUM rechts Isar. The heart cells produced in the laboratory still have the best way to measure electrical activity. In the past, microelectrodes were most commonly used to directly determine the electrical signals of cells, but this process is quite cumbersome and can only be used on a few cells.
Difference between cell types
In addition, not all heart cells are the same. All heart cells are able to contract at their own pace and are forwarded to neighboring cells with electrical signals. On the other hand, the various structures in which the heart is formed, such as the atrium, the cavity or the sinus node, that is, the cells of the "cardiac pacemaker" of the heart, are significantly different from each other, for example, in terms of action potential. The voltage change between the inside and outside of the cell forms a process for controlling cardiac excitation and contraction.
A rhythm disorder caused by a specific region of the myocardium causes the difference to become a shutdown. Generating heart cells from stem cells, scientists today can only affect cells into ventricular cells, atrial cells or cell lymph nodes, and are not very effective. To explore a particular condition, scientists must be precise about the type of individual cell.
Biosensor instead of microelectrode
Daniel Sinnecker and his team, The Heart of Europe magazine, offer possible solutions to problems. Unlike methods such as attaching microelectrodes to cells, scientists use biosensors. These are derived from fluorescent, ieluminous, deep sea jelly proteins. DNA containing these sensor protein "construction plans" is introduced into cardiac cells, and then the protein of the sensor is produced. The labeled heart cells are stimulated with light of a particular wavelength that will produce light at different wavelengths. The exact color of the returned light depends on the voltage difference between the inside and outside of the cell. So one can use a special camera to measure and record the action potential of a single cell.
A special feature of this new approach is that the inserted DNA can be paired with a specific recognition sequence, the so-called promoter. These ensure that sensor protein production is only present in certain types of heart muscle cells. Therefore, only electrical signals from atrial cells, ventricular cells, or sinoatrial node cells can be captured as needed.
Study the possibility of drug toxicity
This approach provides significant improvements over existing cumbersome microelectrode technology. “We can already investigate hundreds of cells a day, not just a small part,†said Chen Zhfen, the first author of the study. “This process can basically be automated and scaled up so that thousands of cells can be studied at the same time.â€
“In the future, we can use our methods to not only study diseases in the laboratory,†Sinnecker said. "We investigate a large number of cells, which means that we can also use this method for drug research. For example, we can investigate whether drugs have a negative impact on the heart muscle." The new program challenge is that sufficient cells must be prepared. Sinnecker and his team are working hard to increase the sensitivity of their methods.
Source: Noble
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