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Updated: Jun 4, 2025
Transplantation of Human Induced Pluripotent Stem Cell-Derived Microglia in Immunocompetent Mice Brain via Non-Invasive Transnasal Route
Published on: May 31, 2022
Human pluripotent stem cell-derived microglia shape neuronal morphology and enhance network activity in vitro
L M L Kok1, K Helwegen1, N F Coveña2
1Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, De Boelelaan, Amsterdam 1081 HV, The Netherlands.
Background:
Microglia, the resident immune cells of the central nervous system, play a critical role in maintaining neuronal health, but are often overlooked in traditional neuron-focused in vitro models.
New Method:
In this study, we developed a novel co-culture system of human pluripotent stem cell (hPSC)-derived microglia and neurons to investigate how hPSC-derived microglia influence neuronal morphology and network activity. Using high-content morphological analysis and multi-electrode arrays (MEA), we demonstrate that these microglia successfully incorporate into neuronal networks and modulate key aspects of neuronal function.
Results:
hPSC-derived microglia significantly reduced cellular debris and altered neuronal morphology by decreasing axonal and dendritic segments and reducing synapse density. Interestingly, despite the decrease in synapse density, neuronal network activity increased.
Conclusion:
Our findings underscore the importance of including hPSC-derived microglia in in vitro models to better simulate in vivo neuroglial interactions and provide a platform for investigating neuron-glia dynamics in health and disease.
