Enabling peristalsis of human colon tumor organoids on microfluidic chips

Peristalsis in the digestive tract is crucial to maintain physiological functions. It remains challenging to mimic the peristaltic microenvironment in gastrointestinal organoid culture. Here, we present a method to model the peristalsis for human colon tumor organoids on a microfluidic chip. The chip contains hundreds of lateral microwells and a surrounding pressure channel. Human colon tumor organoids growing in the microwell were cyclically contracted by pressure channel, mimicking the in vivo mechano-stimulus by intestinal muscles. The chip allows the control of peristalsis amplitude and rhythm and the high throughput culture of organoids simultaneously. By applying 8% amplitude with 8 similar to 10 times min(-1), we observed the enhanced expression of Lgr5 and Ki67. Moreover, ellipticine-loaded polymeric micelles showed reduced uptake in the organoids under peristalsis and resulted in compromised anti-tumor efficacy. The results indicate the importance of mechanical stimuli mimicking the physiological environment when using in vitro models to evaluate nanoparticles. This work provides a method for attaining more reliable and representative organoids models in nanomedicine.

Automated summary

This study presents a method to model peristalsis in human colon tumor organoids on a microfluidic chip. The chip allows the control of peristalsis amplitude and rhythm, and enables high throughput culture of organoids. Results show the importance of mimicking mechanical stimuli in the physiological environment when evaluating nanoparticles in vitro.