Introduction

Human energy metabolism is centrally regulated by the pancreatic islets and the liver. There is an urgent need for a reliable human in-vitro model that can recapitulate this feedback-loop. The combination of human pluripotent stem cell (PSC) differentiation, organoids, and organ-on-chip (OoC) technologies offers a novel toolbox for advanced diabetes disease modeling.

Experimental procedure and methods

We have developed a pump-less recirculation OoC platform that generates a directional, gravity-driven flow using a 3D-tilting platform for multi-organ culture (UK patent application 2110366.8). Human stem cell-derived liver and islet organoids were cultured for 2 weeks on our chip platform as separate or co-culture with the medium flow on top of organoids. The viability of organoids was evaluated by FDA/PI staining on day 14 of culture. Glucose-stimulated insulin secretion (GSIS) and the levels of albumin and urea were measured on days 1 and 14 of culture.

Results and Discussion

Islet and liver organoids stayed viable both alone and in co-culture on the platforms over the period of 2 weeks, confirmed FDA/PI staining. Interestingly, islet organoids on the co-culture system showed improvement in GSIS compared to the mono islet organoids culture (p<0.05 vs mono islet on chip). Consumption of insulin and albumin secretion by liver organoids was improved in the co-culture compared to liver organoids cultured alone on chip.

Conclusion

In our proof-of-concept study, we developed a scalable and easy-to-use pump-less OoC platform for the functional co-culture of islet and liver organoids, enabling the crosstalk between them. Both islet and liver organoids showed improvement in functionality when cultured together. Our platform could have a potential for diabetes disease modeling by combining islet and liver and could be further developed with adding endothelial and immune cells into the chip.