Towards a multi-organ-chip platform combining human liver, pancreatic islets, skeletal muscle and kidney equivalents to study metabolic diseases

Background: In vivo experiments for the study of metabolic diseases are crucial, however limited due to phylogenetic differences between humans and animals. Here, an approach to systemically combine several human organ models to study pathogenesis and therapeutic intervention in metabolic diseases is shown.

Methods: At the size of a microscopic glass slide, the multi-organ-chip consists of two independent microfluidic circuits, representing the blood circulation and the urinary tract. At their interconnection the circuits are separated by a PET membrane, allowing the cultivation of kidney proximal tubule cells. The blood circuit connects the kidney cells with up to 3 additional organ equivalents, each in spatially separated cavities. An integrated on-chip micropump circulates a nutrient solution through the microfluidic channel system. This connection of all organ models enables their cross-talk. The cultivation cavities can be opened at any time during culture, allowing samples to be taken for metabolite analysis.

Results: Co-cultures of human liver spheroids and human pancreatic islets are able to drop glucose levels from high glucose to physiological values within 24h. Glucose homeostasis can be maintained for up to 48h without adding fresh medium to the system. While the insulin level in islet single cultures steadily increases, it stagnates in co-culture with liver spheroids. In order to simulate the in vivo glucose-insulin balance more closely, additional tissue equivalents for skeletal muscle as well as the kidney are envisioned to be cultured in our microphysiological device. Finally, progress on the generation of insulin resistant liver cells will be shown.