Cultured liver cell microreactor might replace animal testing
Finding alternatives to animal testingis an important endeavor. While the practice has been banned in thecosmetic products industry since 2013, it's still a central part ofevaluating the effectiveness and dangers of new medication, withresearchers usually using laboratory rodents to test out their latestdrugs. Now, a team lead by scientists at Germany's Fraunhofer Institute for Cell Therapy and Immunology has created a microbioreactor that has the potential toprovide medication testing using cultured liver cells rather thananimals.
The liver is most important organ whenit comes to removing dangerous toxins from the body, making culturedliver cells a good candidate for testing substance toxicity outsideof the body. But there are difficulties in their use, most notablythe fact that it's very difficult to keep them alive for long periodsof time, making long-term effect tests practically impossible.
Researchers at the Fraunhofer Institutein Potsdam, working as part of the Hepatic Microfluidic Bioreactorproject (HeMiBio), decided to use a microbioreactor to allow forlonger-term observations, providing an environment in which the cellscan survive for as long as four weeks. Furthermore, the device allowsthe researchers to observe how the liver reacts to toxic substancesin real time – a big improvement over existing tests, which usuallyonly observe changes at the end of the process.
The role of oxygen in the metabolicprocess is central to how the microreactor detects reactions to foreign substances. When acell's metabolism is stimulated, oxygen consumption increases.Conversely, if it dies, then its oxygen consumption rate will drop tozero.
When designing the reactor vessel, theresearchers worked to come up with sensor technology that tookadvantage of this, while coping with a high concentration of cellswithout interference giving rise to false or misleading data. Aftersome thought, they decided to use a series of tiny polymer particleshousing a luminescent dye, embedding them in among the liver cells.
When the sensor particles are exposedto monochromatic LED light, the dye they contain emits aphosphorescent glow, exciting individual electrons, raising them tohigh levels of energy. The time required for the electrons to lowertheir energy is affected by the amount of oxygen present in theimmediate environment, meaning that the researchers can use the timethe phosphorescent glow takes to fade to analyze the rate ofmetabolic activity. Looking at the curve of oxygen consumption allowsthe researchers to pinpoint metabolic processes taking place in cellsat specific times, detailing exactly how the cells are reacting to the foreign substance.
Early tests indicate that the microbioreactor could provide a liver-like environment in the lab, but there's still a lot of work to do. The researchers have tested themethod extensively, confirming that it works as intended. Looking forward,they plan to populate it with different combinations of liver cells,fine-tuning the sensors as the work continues.
In the long run, theteam believes that it might be possible to place tissue samples fromdifferent organs into the reactor, recording their reaction toforeign substances during the course of a single test.