Human induced pluripotent stem cell-derived astrocyte and neuron co-culture model for neuroinflammation modeling

Abstract

Access to human neural cells is important for faithful in-vitro neural modeling as animals have innate species gaps. However, primary human cells are difficult to retrieve whereas immortalized human cell lines do not guarantee complete authenticity. Differentiation of human induced pluripotent stem cells (hiPSCs) has emerged as a novel approach to derive faithful human neural cells. Here we differentiated hiPSCs into functional midbrain dopaminergic (mDA) neurons and astrocytes by either a dual-SMAD method or a direct lineage reprogramming method. We found that a co-culture setting was necessary in maturing both the hiPSC-derived neurons and astrocytes. Besides, we showed that the neuron-astrocyte co-culture model was suitable for modeling the astrocyte-driven neuroinflammation. Overall, these hiPSC-derived neural cells represent powerful tools for both basic and translational studies.