TY - JOUR
KW - Assay systems
KW - Neuroimmunology
KW - Neurological models
KW - Phenotypic screening
KW - Tissue engineering
AU - Jiajing Zhang
AU - Yi Wei Lim
AU - Angelica Medina
AU - Yu-Chi Chen
AU - Yining Irene Wang
AU - Martin Carrasco Carvajal
AU - Marc Ferrer
AU - Emily M. Lee
AB - Microglia are the primary resident immune cells of the brain, playing both protective and deleterious roles in neurological diseases, which makes them an enticing therapeutic target. Here we developed a Neural Microglia Integrated Multicellular iPSC-derived Cultured Spheroids (NeuroMIMICS) system that enables measurements of both neural network activity and immune responses using human iPSC-derived microglia, astrocytes, and neurons. We validated microglia functionalities in these neural tri-cultures including phagocytic activity, directed motility, and inflammatory responses. RNAseq analysis revealed a phenotypical acquisition of immune functionality via microglia incorporation, supported by increased cytokine production in spheroids challenged with pathogen-like insults. We then demonstrated that the incorporation of healthy microglia corrected alpha-synuclein A53T-mediated dysfunctional phenotypes in the neural spheroids. This work demonstrates a unique immunocompetent functional neural model that is robust and suited for high-throughput screening, laying the groundwork for its application to accelerate the discovery of new therapeutics for neurological diseases.
BT - Communications Biology
DA - 2026-07-15
DO - 10.1038/s42003-026-10696-w
LA - en
N2 - Microglia are the primary resident immune cells of the brain, playing both protective and deleterious roles in neurological diseases, which makes them an enticing therapeutic target. Here we developed a Neural Microglia Integrated Multicellular iPSC-derived Cultured Spheroids (NeuroMIMICS) system that enables measurements of both neural network activity and immune responses using human iPSC-derived microglia, astrocytes, and neurons. We validated microglia functionalities in these neural tri-cultures including phagocytic activity, directed motility, and inflammatory responses. RNAseq analysis revealed a phenotypical acquisition of immune functionality via microglia incorporation, supported by increased cytokine production in spheroids challenged with pathogen-like insults. We then demonstrated that the incorporation of healthy microglia corrected alpha-synuclein A53T-mediated dysfunctional phenotypes in the neural spheroids. This work demonstrates a unique immunocompetent functional neural model that is robust and suited for high-throughput screening, laying the groundwork for its application to accelerate the discovery of new therapeutics for neurological diseases.
PY - 2026
T2 - Communications Biology
TI - Microglia integrated neural spheroids enable neuroinflammatory responses and correct network dysfunction induced by alpha-synuclein mutation
UR - https://www.nature.com/articles/s42003-026-10696-w
Y2 - 2026-07-20
SN - 2399-3642
ER -