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-4 Pump-less microfluidic device for the functional co-culture of human stem cell-derived islet and liver organoids

Shadab Abadpour, Norway

Postdoctoral Fellow
Transplantation
Oslo University Hospital
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Abstract

Pump-less microfluidic device for the functional co-culture of human stem cell-derived islet and liver organoids

Shadab Abadpour1,3, Aleksandra AA Aizenshtadt1, Chencheng CW Wang1,3, Mathias MB Busek1,2, Alexey AG Golovin2, Justyna JS Stokowiec2, Hanne HS Scholz1,3, Stefan SK Krauss1,2.

1Hybrid Technology Hub, Institute of Basic Medical Science, University of Oslo, Oslo, Norway; 2Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, Norway; 3Department of Transplant Medicine and Institute for Surgical Research, Oslo University Hospital, Oslo, Norway

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.


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