Modeling brain macrophage biology and neurodegenerative diseases using human iPSC-derived neuroimmune organoids

Induced pluripotent stem cells (iPSCs): molecular mechanisms of induction and applications

“…Neurological disorders can also be modeled with brain organoids that can reveal dysfunctional cell-cell interactions and complex disease phenotypes. [294][295][296][297] For example, brain organoids derived from iPSCs of patients with Down syndrome or ASD Fig. 3 Disease modeling with iPSC-derived cells.…”

Myelin organoids for the study of Alzheimer's disease

“…However, the lipid sensing ability of the R47H isoform of TREM2 is impaired (Wang et al, 2015 ). To study the effects of TREM2 and other genetic risk variants specific to microglia, neuroimmune myelinoids can be generated by seeding iPSC-derived microglia onto the myelinoid to allow microglia infiltration and interaction with other cell types in the organoid ( Figure 1D ) (Cerneckis and Shi, 2023a ; Cerneckis et al, 2023 ). Given the major roles that microglia play in clearing myelin debris, recycling lipids, and mediating neuroinflammation in AD, neuroimmune myelinoids will serve as a robust platform to define the interplay between microglia and myelin dysfunction in AD.…”

Developing a human iPSC-derived three-dimensional myelin spheroid platform for modeling myelin diseases

“… 6 , 7 , 8 hiPSC-derived three-dimensional (3D) spheroids or organoids have been used to study brain development and disorders in our group and others. 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 However, it has been difficult to recapitulate mature myelination in these 3D structures. To address this limitation, methods have been developed to generate 3D oligospheres with mature oligodendrocytes and myelination.…”