Multi-Organ Chips – The Patients of Tomorrow?

The liver, nervous tissue or the intestines: all are important human organs that have in the past been tested for their function and compatibility using animal or in vitro test methods. By now, organ-on-a-chip systems, which simulate organ structures on a microscale are gaining momentum. In recent years, TissUse GmbH, a spin-off of the Technical University of Berlin (TU Berlin), has launched multi-organ chip platforms. But that’s not all.

In this interview with MEDICA.de, Dr. Uwe Marx talks about the opportunities this offers for personalized medicine, explains the disadvantages of animal testing and reveals the potential "chip patient" of the future.

What is the structure of the 2-organ and 4-organ chips and how do they work?

Dr.  Uwe Marx: We have developed a synthetic chip the size of a credit card in which micro-channels similar to the human blood vessels connect two or four small chambers to culture miniaturized human 3D organ models for extended time periods. Thanks to an air-operated micro-pump that’s integrated into the chip, we can circulate nutrient solutions or blood with human vascular perfusion through the organ models. This allows stable maintenance of their natural function and interaction for weeks and months. The organ models - in the case of the 4-Organ-Chip that’s the liver, intestine, nervous tissue and kidney for example - are composed of suitable donor cells for use in the chip. We scale down the human organs by a factor of 1: 100,000 (one hundred thousand). We are presently able to build 16 human organ models for chip use. The chips can be used to simulate diseases like diabetes or cancer. You can subsequently use this type of chip as a stand-in for patients to test the efficacy and side effects of new types of drugs. As it the case with real patients, these drugs can be orally or intravenously administered in the intended frequency, e.g. twice daily for several weeks.

What are the disadvantages and limitations of in vitro or animal testing from your perspective?

Marx: The drawback of animal testing is the fact that the biology of animals differs from that of humans, thus foiling meaningful results on the efficacy or side effects of a drug. Previous in vitro testing using human cells or 3D organ models were only able to simulate the response of human tissue, but not their combination in a physiological structure. Today, more than 80 percent of new drugs that test successfully in animals and in vitro fail in final human trials because they reveal previously undetected side effects or they prove ineffective.

How can organs-on-a-chip technology advance personalized medicine?

Marx: Induced pluripotent stem cell technology (iPS) was awarded the Nobel Prize and for the first time has enabled us last year to differentiate different miniaturized organ models using the stem cell of a donor. We were able to successfully cultivate these over two weeks in our 4-Organ-Chip. We previously depended on available tissue from different donors to create the individual organ models. Now we can combine all the organs of any donor on a customized basis on "his or her" chip. We hope that this will also enable us to evaluate the person’s unique reaction to a drug treatment. Ideally, this would facilitate a personalized treatment plan that is customized to the individual patient’s needs.

There are also plans for a human-on-a-chip system in the future. How exactly does this innovation work?

Marx: Nature has equipped the human body with a defined set of dozens of organs to work together in unison. The current working hypothesis of a still small portion of the scientific community focused on modeling complete miniaturized human organs on a chip is that you must physiologically link at least ten of the most important human organs on a chip successfully to mimic the entire human body. Literature refers to these types of chips as human-on-a-chip or body-on-a-chip systems and they don’t exist yet. If it were possible to develop such models and induce diseases at these miniaturized organs on the chips, it would create so-called "chip patients", allowing us to collect the type of data via the chips that we previously collected in clinical trials using humans.

How far are you along in developing this type of chip?

Marx: We will conclude the feasibility studies for our first human-on-a-chip models this year, which we were able to develop thanks to the support of the BMBF funding initiative GO Bio.

Where do you still see difficulties?

Marx: Perfusion and innervation of the organs with nervous tissue still present big challenges.

A glimpse into the future: Could organ-on-a-chip systems fully render animal testing obsolete?

Marx: Our assumption is that future "chip patients" can generate meaningful data for the majority of disease patterns and subsequently replace the respective animal experiments. At the same time, the goal is to significantly scale back Phase 1 and 2 studies on humans and reduce the failure rates of subsequent human studies from 80% to 10%. This would create a paradigm shift in drug development, resulting in patients getting effective, innovative medicines much faster and at a lower cost. This technology reaches its limits as it pertains to diseases that by definition cannot be replicated with a miniaturized organ model that lacks empathy, consciousness, and awareness. This includes mental disorders that cause changes in consciousness and are strictly tied to the exact architecture of the human brain with its total weight of 1.2 - 1.4 kilograms. Still another example is a leg fracture. Even though the chip is able to simulate a model of bone and muscle, it is unable to mimic a full-size leg.