Simulating the Effect of Gut Microbiome on Cancer Cell Growth Using a Microfluidic Device.

The imbalance in the gut microbiome plays a vital role in the progression of many diseases, including cancer, due to increased inflammation in the body. Since gut microbiome-induced inflammation can serve as a novel therapeutic strategy, there is an increasing need to identify novel approaches to investigate the effect of inflammation instigated by gut microbiome on cancer cells. However, there are limited biomimetic co-culture systems that allow testing of the causal relationship of the microbiome on cancer cells. Here we developed a microfluidic chip that can simulate the interaction of the gut microbiome and cancer cells to investigate the effects of bacteria and inflammatory stress on cancer cells in vitro. To test the microfluidic chip, we used colorectal cancer cells, as an increased microbiome abundance has been associated with poor outcomes in colorectal cancer. We cultured colorectal cancer cells with Bacillus bacteria or lipopolysaccharide (LPS), a purified bacterial membrane that induces a significant inflammatory response, in the microfluidic device. Our results showed that both LPS and Bacillus significantly accelerated the growth of colorectal cancer cells, therefore supporting that the increased presence of certain bacteria promotes cancer cell growth. The microfluidic device included in this study may have significant implications in identifying new treatments for various cancer types in the future.

The Applications and Challenges of the Development of In Vitro Tumor Microenvironment Chips.

The tumor microenvironment (TME) plays a critical, yet mechanistically elusive role in tumor development and progression, as well as drug resistance. To better understand the pathophysiology of the complex TME, a reductionist approach has been employed to create in vitro microfluidic models called "tumor chips". Herein, we review the fabrication processes, applications, and limitations of the tumor chips currently under development for use in cancer research. Tumor chips afford capabilities for real-time observation, precise control of microenvironment factors (e.g. stromal and cellular components), and application of physiologically relevant fluid shear stresses and perturbations. Applications for tumor chips include drug screening and toxicity testing, assessment of drug delivery modalities, and studies of transport and interactions of immune cells and circulating tumor cells with primary tumor sites. The utility of tumor chips is currently limited by the ability to recapitulate the nuances of tumor physiology, including extracellular matrix composition and stiffness, heterogeneity of cellular components, hypoxic gradients, and inclusion of blood cells and the coagulome in the blood microenvironment. Overcoming these challenges and improving the physiological relevance of in vitro tumor models could provide powerful testing platforms in cancer research and decrease the need for animal and clinical studies.

An Inexpensive Cardiovascular Flow Simulator for Cardiac Catheterization Procedure Using a Pulmonary Artery Catheter.

Cardiac catheterization associated with central vein cannulation can involve potential thrombotic and infectious complications due to multiple cannulation trials or improper placement. To minimize the risks, medical simulators are used for training. Simulators are also employed to test medical devices such as catheters before performing animal tests because they are more cost-effective and still reveal necessary improvements. However, commercial simulators are expensive, simplified for their purpose, and provide limited access sites. Inexpensive and anatomical cardiovascular simulators with central venous access for cannulation are sparse. Here, we developed an anatomically and physiologically accurate cardiovascular flow simulator to help train medical professionals and test medical devices. Our simulator includes an anatomical right atrium/ventricle, femoral and radial access sites, and considers the variability of arm position. It simulates physiological pulsatile blood flow with a setting for constant flow from 3 to 6 L/min and mimics physiological temperature (37°C). We demonstrated simulation by inserting a catheter into the system at radial/femoral access sites, passing it through the vasculature, and advancing it into the heart. We expect that our simulator can be used as an educational tool for cardiac catheterization as well as a testing tool that will allow for design iteration before moving to animal trials.