image: Creating enteric neuro-epithelial co-cultures in a microfluidic device. a Intestinal epithelial cells are located on the luminal lining of the gut. Upon receiving physical or chemical stimuli, intestinal epithelial cells communicate with enteric neurons such as IPANs in the myenteric plexus which is located between the circular and longitudinal layers of muscularis externa of the gut. Neuro-epithelial communications trigger expansion or contraction of the muscle layers in the gut. b Our microfluidic culture system was designed to recapitulate aspects of the neuro-epithelial interactions observed in vivo. This culture platform allowed to define and visualize neuro-epithelial contacts.
Credit: The authors
Epithelial cells and sensory neurons communicate through neuro-epithelial connections in the GI tract, essential for major senses and digestion. Studying these interactions has been complex due to the differing needs of epithelial cells and neurons. This paper introduces a novel microfluidic device for co-culturing intestinal epithelial cells and enteric neurons, overcoming previous challenges. The device's innovative design enables detailed observation and study of neuro-epithelial interactions, marking a significant advancement in understanding gastrointestinal functions and potentially contributing to improved healthcare solutions for related disorders.
In a study published on 14 November 2023, in the journal Microsystems & Nanoengineering, a significant advancement for biomedical research has been made. A team from Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA developed a novel microfluidic device that mimics the intricate neuro-epithelial connections in the human gut.
The research introduces an advanced microfluidic device designed to simulate the complex neuro-epithelial connections in the human gut. This device features two compartments that enable the co-culture of enteric neurons and intestinal epithelial cells from human organoids. The neuronal compartment contains intestinal myenteric neurons, including intrinsic primary afferent neurons (IPANs) from transgenic mice. These neurons extend projections into microgrooves, often contacting adjacent epithelial cells and enhancing the density and directionality of neuronal projections. This design allows for detailed study of gut neuron and epithelial cell interactions in a natural-like environment. It provides a unique opportunity to understand gut neuro-epithelial dynamics, contributing to our knowledge of gut physiology and paving the way for further studies in other organs.
The researchers on the project, stated, "This microfluidic device is a leap forward in our ability to understand and potentially treat a range of gastrointestinal disorders. It allows us to closely study the interactions between gut neurons and epithelial cells in a controlled environment."
The device's ability to model gut neuro-epithelial connections has significant implications for medical research and treatment. It provides a platform for studying the gut's response to various stimuli and diseases, potentially leading to better understanding and treatment of conditions like irritable bowel syndrome and other functional gastrointestinal disorders. Moreover, the technology could be adapted to study other organs and systems, widening its impact.
The device's capacity to simulate gut neuro-epithelial connections carries substantial implications for medical research and treatment. It offers a platform to study the gut's reactions to different stimuli and diseases, potentially enhancing the understanding and treatment of conditions such as irritable bowel syndrome and other functional gastrointestinal disorders. Furthermore, this technology could be adapted to investigate other organs and systems, broadening its impact.
Reference
Funding information
TheDERIVE, Center for Biomedical Discovery, and Cells to Cures Initiative at Mayo Clinic;
The NIH grants (R21NS118790, R01DK129315, DP2AT010875, R01DK123549, P30DK084567, KL2TR002379);
The Skoll Foundation.
DOI: 10.1038/s41378-023-00615-y
Original URL: https://doi.org/10.1038/s41378-023-00615-y
About Microsystems & Nanoengineering
Microsystems & Nanoengineering is an online-only, open access international journal devoted to publishing original research results and reviews on all aspects of Micro and Nano Electro Mechanical Systems from fundamental to applied research. The journal is published by Springer Nature in partnership with the Aerospace Information Research Institute, Chinese Academy of Sciences, supported by the State Key Laboratory of Transducer Technology.
Journal
Microsystems & Nanoengineering
Article Title
Modeling gut neuro-epithelial connections in a novel microfluidic device
Article Publication Date
14-Nov-2023
COI Statement
The authors declare that they have no conflicts of interest.