Hepatogenic differentiation of mesenchymal stem cells using microfluidic chips.

Directional induction and differentiation of mesenchymal stem cells (MSCs) is very important to clinical therapy, but the mechanisms that govern differentiation are not well understood. However, traditional plate culture cannot precisely control cellular behavior because cells take up substances while secreting cytokines and wastes. Here, we used a microfluidic device to culture MSCs inside a microchamber. Hepatic differentiation medium was perfused to evaluate the ability of MSCs to differentiate toward hepatic cells on the chip. Parallel differentiation on 96-well plates was used to provide a detailed comparison of the differences between the two culturing methods. After treatment for 4 weeks, differentiated cells from both groups could express hepatocyte-specific markers, including alpha-fetoprotein, tyrosine aminotransferase, and albumin. The bioactivity assays revealed that these hepatocyte-like cells could uptake lipoprotein, but cells that differentiated on the chip showed more positive signals than the cells cultured on plates. Our results indicated that a microfluidic platform might be a potential tool for cost-effective and automated cell culture, and have potential applications in reliable cell-based screens and assays.