Human iPSC-derived glia models for the study of neuroinflammation

Abstract

Neuroinflammation is a complex biological process that plays a significant role in various brain disorders. Microglia and astrocytes are the key cell types involved in inflammatory responses in the central nervous system. Neuroinflammation results in increased levels of secreted inflammatory factors, such as cytokines, chemokines, and reactive oxygen species. To model neuroinflammation in vitro, various human induced pluripotent stem cell (iPSC)-based models have been utilized, including monocultures, transfer of conditioned media between cell types, co-culturing multiple cell types, neural organoids, and xenotransplantation of cells into the mouse brain. To induce neuroinflammatory responses in vitro, several stimuli have been established that can induce responses in either microglia, astrocytes, or both. Here, we describe and critically evaluate the different types of iPSC models that can be used to study neuroinflammation and highlight how neuroinflammation has been induced and measured in these cultures.

Keywords: Astrocytes; Co-culture; Cytokines; Induced pluripotent stem cells; Microglia; Monoculture; Neural organoids; Neuroinflammation; Xenotransplantation; iPSC.

Fig. 1

Overview of culture models for iPSC-microglia and iPSC-astrocytes. A In recent years, numerous protocols have been developed to differentiate iPSC to microglia and astrocytes, of which a selected number is mentioned here. B PSC-derived cell conditioned media has been used to investigate its effect on other CNS cell types. Here we list all the studies mentioned in the review. C iPSC-derived CNS cells can also be studied in co-cultures of two or three different cell types. D Several strategies for the generation of 3D neural organoids have been established and a number of representative protocols are highlighted here. E Recently, methods to transplant human pluripotent stem cell-derived microglia and astrocytes into rodent brains have been established. The lists of protocols mentioned in this figure are not exhaustive