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Chunk #19 — Patient hiPscs-Derived Brain Cells for Modeling Schizophrenia — Modeling Regional Specificity and Circuitry

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Prospects for Modeling Abnormal Neuronal Function in Schizophrenia Using Human Induced Pluripotent Stem Cells.
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Although organoids have yet to be applied to SZ, their potential for modeling neural developmental and electrophysiological anomalies is obvious. Much work remains, however, to adequately model circuit development and contributions of non-neural cells to SZ pathology. Currently, brain organoids contain only relatively immature neurons and non-reactive astrocytes, with oligodendrocytes and microglia still lacking. Potential injection of hiPSC-derived oligodendrocytes and microglia (discussed in the section “Co-culture System”) has promise for incorporation into organoid tissue, and the potential to recapitulate exciting in vivo findings that SZ patient hiPSC-derived glial cells function differently when injected into a mouse brain (Windrem et al., 2017), but differences in growing conditions and developmental requirements still pose major challenges in vitro.