Enables complex metabolic processes within the human body to be analysed
Using the compact multi-organ chip (comparable in size to a Euro coin), and those of three separate microcircuits, researchers can study the regeneration of certain kidney cells (© Fraunhofer IWS)
Fraunhofer Institute researchers have developed a promising alternative to using animals in experiments – a mini-organism inside a chip, which enables complex metabolic processes within the human body to be analysed realistically.
Researchers at the Dresden, Germany-based institute, working jointly with the Institute for Biotechnology at the Technical University (TU) of Berlin, say their solution could render the use of animal-based experiments superfluous in medical research because it faithfully replicates complex metabolic processes in the human body with startling accuracy.
'Our system is a mini-organism on a 1:100,000 scale to the human being,' says Frank Sonntag of the Fraunhofer Institute for Material and Beam Technology IWS.
Human cells from various organs can be applied to several different positions within the chip. The researchers obtained the cells from blood donations that were made available for research purposes. These 'mini-organs' are connected to each other through tiny canals. 'This way we simulate human blood circulation,' Sonntag explains.
Our system is a mini-organism on a 1:100,000 scale to the human being
Working much like the human heart, a micro-pump continuously transports liquid cell culture medium through infinitesimal micro-channels. The IWS researchers can modify the exact configuration of the chip, i.e. the number of mini-organs and the connection to the micro-channels, specifically to different sets of questions and different applications. With the chip, it is possible to test both the active ingredients in new medicines, and also study cosmetics for their skin tolerability.
The concept of combining various cell samples with fluid channels has been around for a long time, but this new system has two distinct advantages over previous approaches. First, the microfluidic system is miniaturised and the pump is capable of channelling the tiniest flow rates of less than 0.5 microlitres per second (µl/s) through the channels.
'This means the relationship between cell sample and liquid media is authentic,' says Sonntag. If this ratio is incorrect, imprecise results will ensue.
Second, the microfluidic system ensures that there is a constant flow of liquid cell culture medium. This is important, since some types of cells can only present 'body-like' morphology if they are stimulated by a current or flow.
To test the effect of a substance, the scientists initially loaded various cell samples onto the chip. Then the active ingredient to be tested was added through the medium for the cell sample of the organ into which the substance would be introduced in the real human body. For example, they could include the cells of the intestinal lining. The same metabolic responses are then processed on the chip just like in the human organism.
'We use cell samples from various sexes and ethnicities. We can set variations in body size and weight as desired on a scale of 1:100,000,' says Sonntag.
The scientists can see exactly which metabolic products form within specific cell samples, and what effects they might have on other cells. The results are ultimately even more predictive than those of animal-based experiments because the effects on the body of a mouse or a rat cannot be applied to human beings at a 1:1 ratio.
The artificial organism is already being used by scientists in the cosmetics industry.
But, in addition to research on active ingredients, there is also another potential application. 'We know today that certain kidney cells, the endothelial cells, play a key role in almost every kidney disease. With the in vitro tests to date, there was always the problem that the endothelial cells worked only under current conditions. Here, our multi-organ chip could offer a test environment that would allow you to observe how cells regenerate following an injury,' says Sonntag.