Selective control of liver and kidney cells migration during organotypic cocultures inside fibronectin-coated rectangular silicone microchannels.

ABSTRACT

In this work, the behaviors of embryonic liver and kidney explants were studied inside rectangular polydimethylsiloxane (PDMS) microchannels. The organs were cultured under monoculture and coculture conditions on PDMS coated with or without fibronectin. The results demonstrated that the migration of cells from both organs is dependent on culture conditions and thus can be selectively controlled. In liver monocultures without fibronectin, cell migration in the microchannels resulted in the formation of a dense 3D tissue. Fibronectin reduced liver cell migration and enhanced the emergence of cells demonstrating typical hepatocyte phenotypes at the vicinity of the explant. The migration rate in liver-liver cocultures, with and without fibronectin, was roughly twice the rate of cells under monoculture conditions. In cocultures, both livers merged to form a large tissue in which the two initial organs could not be identified. In kidney monocultures, with and without fibronectin, we did not observe any migration inside the microchannels. Contrary to liver cells, kidney cell migration was triggered when both fibronectin coating and coculture with liver or another kidney explant were used. The migration was more largely observed in coculture with liver when compared to kidney-kidney cocultures. In the case of liver-kidney coculture with fibronectin, the progression of the kidney cells inside the microchannels appears as a displacement of the entire kidney explant in the direction of the liver. The liver cells did not move in those cases. After contact, we observed a complete merging of both liver and kidney explants. In contrast, for liver-kidney cocultures without fibronectin, only the liver moved toward the kidney.