Perfusion and modification of microbiome in lumen of intestinal organoids

Intestinal organoids have found application as a research tool to study intestinal function in health and disease, but is it feasible for these biological models to replicate gastrointestinal motility and microbiome stability? One of the limitations to use organoids in general is accessing their lumens. Adding microbiome, especially strictly anaerobic bacteria, is technically very challenging and many techniques are being developed to overcome this barrier. This is a recent paper from Ginga et al. at the Georgia Institute of Technology modeling human intestinal organoids (HIO), of which the contents can be accessed and regulated by utilizing a perfusion system.

The perfusion system regulated the luminal environment and controlled the luminal volume while maintaining organoids in their closed 3D structure. Cellular response of the perfused organoids emphasized the importance of mimicking physiological conditions. For example, an E.coli-injected HIO in a Static luminal environment resulted in the loss of epithelium structural integrity. In contrast, perfusion organoids with E.coli increased the epithelial thickness approximately two times and improved the structural integrity and the polarization of the epithelium. Moreover, luminal perfusion enhanced the HIO functional maturation shown by higher expression of DPPIV (a digestive enzyme).

The perfusion technology of this study can also be used for developing more complex in vitro models as well as other biological systems. 

Strong points :
+ Higher temporal control of luminal content using a pressure-based pump
+ Multi-focal imaging and analysis of the bacterial content
+ Robust perfusion

Nothing is perfect, some improvement points:
– Perfusion is short with a high chance of contamination
– Limited perfusion-induced cyclic strain compared to some intestine-on-chip devices
– Despite of higher throughput compared to previous efforts, this system is still more limited than other complex in vitro models
– Lack of vehicle-injected or perfused control without E-coli
– Comparison between imaging during perfusion and pre-/post-perfusion is not feasible
– Co-culture with autologous cell types for personalized medicine applications

Contact us if you want to know more about this system or similar technologies.

Link to paper https://www.mdpi.com/2072-666X/13/1/131.

Ginga, N.J., et al., Perfusion System for Modification of Luminal Contents of Human Intestinal Organoids and Realtime Imaging Analysis of Microbial Populations. Micromachines, 2022. 13(1): p. 131. 

This article is reproduced under https://creativecommons.org/licenses/by/4.0/
The images in this post were modified for better clarity (images from different figures were put together), and the data were processed by AZAR Innovations