12 March 2015

"Heart-on-a-chip" will facilitate drug development


The surface of the "heart-on-a-chip" is covered with fabric formed human cardiomyocytes,
derived from induced pluripotent stem cells.
In the future this system will be able to replace animal models
in the development of drugs.

Researchers at the University of California at Berkeley, working under the supervision of Professor Kevin Healy (Kevin Healy), developed the so-called "heart on a chip". The device is a chip with a length of about 2.5 cm, the surface of which is pulsing system of cardiomyocytes, representing an effective model of the fabric of the human heart, is suitable for screening of drugs and study of their toxicity.

The authors note a high degree of failure when using animal models to predict the response of cardiac muscle man on experimental drugs. The main reason for this are fundamental differences in the biology of the species. For example, man and other species vary greatly in number and structural parameters of ion channels, which move emitted by the cells of the heart's electrical impulses. These channels are targets of many drugs for the treatment of diseases of the heart, therefore, interspecific differences often lead to inefficient expensive experiments do not provide obtain reliable data on the toxicity of the drug to humans.

This problem can be solved with the help of the designed model for the creation of which used human induced pluripotent stem cells (IPSC). Derived cardiomyocytes seeded on a specially formed surface of the chip, the three-dimensional structure which reflects the geometry and relative position of the connective fibers in the fabric of the human heart. Thanks to this special structure of the cell was located parallel to each other and formed a multi-layer culture.

As supporting the viability of the heart muscle of blood vessels were located on both sides of the covered cell zone of the microfluidic channels, which delivers nutrients and tested drugs. In the future, these channels can be used to monitor the removal of cell waste products.


These records are used to create the system of the "organ-on-a-chip".

Within 24 hours of placing on the chip surface cardiomyocytes has begun to decline with frequency 55-80 beats per minute, which corresponds to the heart rate of a healthy adult.

To check the efficiency of the system, the researchers used it to monitor the reaction of the cells on four well-known drug for the treatment of heart disease: isoproterenol, E-4031, verapamil and metoprolol. To assess the reaction to the effects of drugs used change of rate cuts.

The obtained results are well predicted based on known data about the effects of drugs. For example, lasting 30 minutes exposure to isoproterenol, used to treat bradycardia (slowing of the heart rate), increased rate from 55 to 124 beats per minute.

The video shows the human heart muscle grown from induced pluripotent stem cells before and after exposure to isoproterenol. After 30 minutes after exposure to the drug, the frequency of contractions of cardiomyocytes increases is evident even without measurements.

The developers note that they have created a "heart-on-a-chip" can be adapted to study different human genetic disease and personalized screening reactions to drugs. They are also studying the possibility of applying the system for simulation of multi-organ interactions (see article "Homunculus grow heart" is far from the first multi-organ "human on a chip", in this case, the Russian production).

Article Anurag Mathur et al. Human iPSC-based Cardiac Microphysiological System For Drug Screening Applications published in the journal Scientific Reports.

Eugene Ryabtsev
The portal of "Eternal youth" http://vechnayamolodost.ru on materials of the University of California – Berkeley:
Bioengineers put human hearts on a chip to aid drug screening.

12.03.2015

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