Protocol for generating and using human iPSC-derived microglia-containing air-liquid-interface cortical organoid cultures

  • Marta Cañizares Luna
  • , Mayte Mars
  • , Channa E Jakobs
  • , Christiaan F M Huffels
  • , Arthur Ermakov
  • , Elly M Hol
  • , R Jeroen Pasterkamp*
  • *Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Here, we present a protocol for generating long-term microglia-containing air-liquid-interface cortical organoid (MG-ALI-CO) cultures. This approach minimizes necrotic core formation, a common limitation of extended organoid cultures, favoring microglia survival and homeostasis. We describe steps for generating air-liquid-interface cortical organoids (ALI-COs), integrating macrophage precursors, and maintaining MG-ALI-COs. Additionally, we outline several experimental analyses of MG-ALI-COs, including immunostaining, imaging, and patch-clamp electrophysiological recordings. This model provides a physiologically relevant system to investigate human neuroimmune interactions in a 3D brain-like environment.

Original languageEnglish
Article number103915
JournalSTAR protocols
Volume6
Issue number3
Early online date30 Jun 2025
DOIs
Publication statusPublished - 19 Sept 2025

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