@article{bibcite_8751, keywords = {Assay systems, Neuroimmunology, Neurological models, Phenotypic screening, Tissue engineering}, author = {Jiajing Zhang and Yi Wei Lim and Angelica Medina and Yu-Chi Chen and Yining Irene Wang and Martin Carrasco Carvajal and Marc Ferrer and Emily M. Lee}, title = {Microglia integrated neural spheroids enable neuroinflammatory responses and correct network dysfunction induced by alpha-synuclein mutation}, abstract = {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.}, year = {2026}, journal = {Communications Biology}, month = {2026-07-15}, issn = {2399-3642}, url = {https://www.nature.com/articles/s42003-026-10696-w}, doi = {10.1038/s42003-026-10696-w}, language = {en}, }