Schematic of the multi-tissue modeling approach. The three cell-specific reconstructions are combined into a multi-tissue model by connecting them all to a new blood compartment. Metabolites enter the model through the extra-system through exchange reactions. Metabolites are then imported into the different cells through gene associated intercellular transporters and/or free diffusion. For differentiating the cell-specific models, all reactions in the model were annotated with [a], [h], [m], and [bl] for the AM, HM, MM and blood compartment, respectively.