A model of low-temperature water transport for hepatocyte spheroids

Spheroids are multicellular aggregates that exhibit a more tissue-like morphology and function when compared to monolayer cultures of the same cells. Hepatocyte spheroids are presently under investigation for use of an artificial liver. The ability to cryopreserve hepatocyte spheroids is essential for their clinical and commercial application. A multicompartment model was formulated to predict water content as a function of temperature during freezing. The theoretical predictions of water transport indicate that there will be spatial differences in water content of the spheroid during freezing and that due to the rapid decrease in water transport with decreasing temperature, the undercooling of the intracellular solution during freezing will increase steadily. These results indicate that conventional freezing of hepatocyte spheroids will be difficult to accomplish due to transport limitations in the spheroids.