Human pluripotent stem cell-derived microglia shape neuronal morphology and enhance network activity in vitro

L. M.L. Kok, K. Helwegen, N. F. Coveña, V. M. Heine*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Article number110354
Pages (from-to)1-8
Number of pages8
JournalJournal of Neuroscience Methods
Volume415
Early online date25 Dec 2024
DOIs
Publication statusE-pub ahead of print - 25 Dec 2024

Bibliographical note

Publisher Copyright:
© 2025 The Authors

Keywords

  • hPSC
  • Human in vitro modelling
  • Microglia-neuron co-culture
  • Multi-electrode arrays

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