Ex vivo obesity research thanks to the adipose-on-chip system

Ex vivo studies of human obesity without animal testing? The Adipose-on-Chip system offers a solution that allows scientists to gain better insights into various obesity-linked secondary diseases and comorbidities in the future.

In this MEDICA.de interview, Professor Peter Loskill explains how adipose-on-chip systems can advance obesity research.

How do adipose-on-chip systems work?

Prof. Peter Loskill: Adipose-on-chip includes a microphysiological platform. It is a polymer module that contains microfluidic channels and chambers and mimics the microenvironment of adipose tissue, including blood vessel perfusion. Adipose tissue is then built up on these modules. The adipose tissue is obtained from patient biopsies – by liposuction, for example - and the isolated cells are integrated into the systems. The tissue is cultivated ex vivo (outside the body) and subsequently studied for responses to stimuli and drugs. This process facilitates experiments to understand adipose tissue and studies pertaining to associated diseases.

Adipose-on-chip systems can essentially be used as models of the human organ. This enables us to address questions such as what happens when you bring the adipose tissue into a state of disease? How does adipose tissue affect other organs and how do drugs impact adipose tissue? Can you manipulate adipose tissue? What are the side effects of drugs that are initially intended to treat other organs or diseases?

How does the new mix-and-match system differ from other organ-on-a-chip systems?

Loskill: There are a variety of organ-on-a-chip systems on the market. However, essentially no models specifically target adipose tissue research. In recent years, we introduced individual systems, and this new system is an advancement of the former. It enables us to replicate all cellular components of adipose tissue. Aside from the fat cells – the adipocytes-, we also integrate stromal cells and stem cell-like progenitor cells. Immune cells are another key aspect of adipose tissue biology. The mix-and-match system allows us to choose the cell types we want to integrate on the chip and to study the impact the individual cell types have on the function of the tissue as a whole. In doing so, we can assess whether the tissue is still functional when we leave out different cells or explore the changes when certain cells are brought into a disease state.

How can you simulate different aspects of obesity via the chip?

Loskill: Chronic inflammation in adipose tissue is one disease that is linked to obesity. We can recreate this inflammation on a chip by integrating the immune cells and different compositions of immune cells. It’s also possible to set up a patient-specific disease model by harvesting tissue directly from obese patients. By leveraging simulations with the adipose-tissue-on-chip, we can study the obesity phenotype, meaning the appearance of an organism shaped by hereditary predisposition and environmental factors.

What role could chip systems play in the future of medical research?

Loskill: Organ-on-a-chip systems allow us to model more complex human biology structures outside of the human body. Traditionally, one would have to use animal testing, which comes with ethical questions besides differing from human systems. Organ-on-a-chip systems give us the option of conducting experimental research on human models without ethical concerns.

However, it’s important to note that these are still developments, not completed research projects. These systems can not replace animal testing overnight. To get to this point, the process still needs time and extensive development, but we are very optimistic that the chip models could reduce the need for animals in experiments in the future.

What new opportunities does the chip open as it pertains to lipid metabolism research?

Loskill: Obesity research is interested in drugs that target the adipose tissue directly. It also explores the signals adipose tissue sends to other organs and studies how this communication could be interrupted or changed. Drug research not only explores how medications affect the adipose tissue but also analyzes whether they are stored or metabolized more intensively in adipose tissue. This is just one of the numerous examples that pertain to clinical or academic research.

How can chip platforms accelerate personalized medicine?

Loskill: Organ-on-a-chip systems, including adipose-on-chip systems, are microscale devices that handle small volumes. This means we obtain an adipose tissue sample from the patient and subsequently yield multiple organ-on-a-chip systems that are tailored to the patient’s specific needs. It allows us to test the individual responses to stimuli or drug effectiveness in a more personalized manner.