Inflammatory Intestinal Disease Model on Microfluidic Chip

Posted by Vivian creative on August 19th, 2022

It's increasingly recognized that the human microbiome is associated with cancer, autoimmune diseases, infections, inflammatory diseases, and many other diseases. However, it's not easy for researchers to figure out the mechanism in vitro. The main issue occurs when researchers try to culture target bacteria and human cells in the same cell culture dish to understand their interactions with each other. That is, bacteria would overwhelmingly grow and kill human cells, and what's more, bacteria, especially those that live in the intestinal lumen, are anaerobic, meaning their living condition would also kill aerobic human cells.

To address this issue, researchers attempted to develop a microfluidic chip years ago, with the aim of enabling the co-culture of bacteria and human epithelial cells. The microfluidic device was designed with two separated compartments—one to culture vascularized human intestinal epithelium and the other to culture complex microbiome. As for the oxygen condition problem, researchers made bacteria expose to a low oxygen condition by culturing the whole device in a custom anaerobic chamber, meanwhile creating an oxygen gradient so that human cells can survive. This intestine-on-a-chip model makes it possible for researchers to understand the interactions between the human intestine and bacteria in vitro.

Building on this microfluidic chip, researchers at Harvard obtain genetic changes underlying environmental enteric dysfunction (EED), a serious childhood inflammatory intestinal disease. The condition mostly strikes millions of children in low-income nations, possibly causing malnutrition, impaired cognitive development, and stunted growth. The lack of in vitro model of EED captures the attention of Harvard researchers who recognize that their microfluidic intestine-on-a-chip model can help physically and genetically understand this disease and develop therapeutics for it.

Thus, the first in vitro model of the EED was developed on the microfluidic chip. The device is built with two microfluidic channels. The inner surface of one channel is covered with endothelial cells, representing intestinal blood vessels, and the other is lined with intestinal epithelial cell samples obtained from EED patients to simulate the intestine. Then, when the fluid enriched with nutrients flows through the blood vessel channel, nutrients can reach the intestinal cells through a permeable membrane between these two channels.

To find out how the EED affects the intestinal functions of patients, including the digestive system, nutrients absorption, and anti-infective ability, researchers set up a controlled microfluidic device, the intestinal channel of which is lined with healthy cells. As a result, a large number of genes of the EED microfluidic chips displayed changes in gene expression, especially after researchers remove certain nutrients from the nutrient fluid. Moreover, with the appearance of inflammation, intestinal barrier dysfunction, and reduced nutrient absorption n intestinal cells, the microfluidic chip also models the symptoms of the inflammatory intestinal disease that happened to human EED patients.

In summary, this first organ-chip model of EED is significantly important for understanding the molecular, genetic, and nutritional bases of the disease and may provide insights into developing candidate therapeutics for such intestinal injuries. In addition to environmental enteric dysfunction, intestine chips are latent to recreate complex states for many other diseases in clinic applications, making it possible to assess digestion, absorption, and allergic reactions to different nutrients in specific patients.