Article by Vanessa Li & Roberta Lock
Using Tissues-on-a-Chip to Study Obesity
Autologous Human Immunocompetent White Adipose Tissue-on-Chip, Advanced Science, 2022
Julia Rogal et al., Peter Loskill Lab
Obesity is a condition defined by an excess amount of body fat and is a growing disorder that leads to a variety of chronic diseases. However, it is challenging to study white adipose tissue (WAT) (a type of fat tissue) in the laboratory for the development of obesity therapies. This study uses an organ-on-a-chip platform to model the pivotal functions of WAT to allow for a greater understanding of WAT-related diseases.
What did these researchers do?
In this study, a white adipose tissue-on-a-chip model was developed to study obesity and associated diseases. The researchers designed a custom chip that holds white adipocytes (fat cells) alongside immune cells and hydrogel, and has a media channel that allows for the perfusion of nutrients and immune cells. The combination of cells and channel in this model allows for the study of not only WAT but also its interaction with their environment and the immune system. In testing this model, it was determined that the key functions of mature adipocytes (storage and release of energy, endocrine function, and responsiveness to inflammatory stimulation) were preserved, and the model is well suited to study immune responses, which are both necessary for studies revolving around obesity.
Immunofluorescent Stain of Fat (Green) and Immune (Pink) Cells in Tissues
Why is this important?
As of 2016, 13% of the world’s adult population was obese, and this number is only growing. In the body, there is a close interaction between immune cells and adipose tissue. As adipocytes expand in number and size from over-nutrition, it leads to inflammatory events that result in long-term health consequences. In fact, obesity increases the risks of diseases such as type 2 diabetes, cardiovascular and neurodegenerative diseases, and 31 different types of cancers. Previously, there were no adequate models to study obesity in the laboratory because white adipocytes are large in size, buoyant, and fragile. Tissue models are sparse and those that exist were unable to capture many of the biological functions that are vital to studying the underlying processes involved in diabetes and other related diseases, such as vascular perfusion, cell-cell interaction, and immune components. Thus, the organ-on-a-chip platform developed in this study provides a more accurate model to study pivotal WAT functions.
How did the researchers do this?
A microfluidic platform was customized to allow for the integration of WAT. Specifically, two layers were generated with PDMS (a biocompatible polymer), separated by a semi-permeable porous membrane. The bottom layer had patterns that formed eight individual tissue compartments while the top layer connected them by a channel that allowed for the perfusion of media. Mature adipocytes used in the study were isolated from skin biopsies, and the monocytes and macrophages were magnetically sorted and derived from peripheral blood mononuclear cells. These cells were encapsulated in a synthetic hydrogel mix and seeded into the tissue chamber. After this, many tests were run to assess the validity of the chip in its ability to mimic the functions of WAT in the body. This includes assessing cell viability and morphology over a short period of time, testing the unique functions of the different cell types, and evaluating cell responses to a variety of drugs.
What comes next?
The WAT-on-chip model provides a promising model to understand obesity as well as its therapeutic treatments. However, the model itself could be further explored and modified to more accurately mimic the human body such as by considering the health state of the tissue donor. Many donor tissues are received following weight loss and thus may potentially have a compromised health state. Additionally, a concern mentioned in this study is the use of PDMS. PDMS absorbs small hydrophobic molecules and could lead to interference in any related studies such as drug testing. As a result, the impact of this material and potential substitutes could be studied as a next step. Also, this model is a powerful tool to study human metabolism and could allow for the development of a myriad of diabetes-related treatments. Because of the way this chip is constructed, it paves the way for personalized and precision medicine applications that allow for therapies to be customized to the individual. The next time you see an obesity treatment in the pharmacy, it may have been developed using this on-a-chip technology!