TY - JOUR
KW - iPSC-derived 3D models
KW - Microglia
KW - microphysiological systems (MPS)
KW - neural organoids
KW - New Approach Methodologies (NAMs)
AU - Alex Rittenhouse
AU - Caroline Krall
AU - Jesse Plotkin
AU - Dowlette-Mary Alam El Din
AU - Breanne Kincaid
AU - Jason Laird
AU - Lena Smirnova
AB - Microglia, essential for brain development, homeostasis, and neuroinflammation, originate from the yolk sac during embryogenesis and migrate into the developing brain. Because of this developmental origin, many brain organoid models naturally lack microglia and require co-culture. To address this issue, we developed a microglia-integrated brain organoid model (immune-competent brain microphysiological system, μbMPS) by aggregating hiPSC-derived neural and microglia progenitors in U-bottom 96-well plates, allowing controlled and reproducible incorporation of microglia progenitors. We demonstrated that microglia integrated, matured, and survived long-term in the neural environment without the need for costly exogenous microglia-specific growth factors or cytokines. We maintained microglia-containing organoids for over 9 weeks, demonstrating functional activity, phagocytosis, and neuroinflammatory responses. The μbMPS also exhibited enhanced neuronal activity and maturity, providing a scalable, reproducible model for neurodevelopment, disease modeling, and neurotoxicology research.
BT - Frontiers in Cellular Neuroscience
DA - 2025-10-02
DO - 10.3389/fncel.2025.1616470
LA - English
N2 - Microglia, essential for brain development, homeostasis, and neuroinflammation, originate from the yolk sac during embryogenesis and migrate into the developing brain. Because of this developmental origin, many brain organoid models naturally lack microglia and require co-culture. To address this issue, we developed a microglia-integrated brain organoid model (immune-competent brain microphysiological system, μbMPS) by aggregating hiPSC-derived neural and microglia progenitors in U-bottom 96-well plates, allowing controlled and reproducible incorporation of microglia progenitors. We demonstrated that microglia integrated, matured, and survived long-term in the neural environment without the need for costly exogenous microglia-specific growth factors or cytokines. We maintained microglia-containing organoids for over 9 weeks, demonstrating functional activity, phagocytosis, and neuroinflammatory responses. The μbMPS also exhibited enhanced neuronal activity and maturity, providing a scalable, reproducible model for neurodevelopment, disease modeling, and neurotoxicology research.
PY - 2025
T2 - Frontiers in Cellular Neuroscience
TI - Microglia-containing neural organoids as brain microphysiological systems for long-term culture
UR - https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2025.1616470/full
VL - 19
Y2 - 2025-10-31
SN - 1662-5102
ER -