TY  - JOUR
AU  - Panagiotakopoulou, Vasiliki
AU  - Welzer, Marc
AU  - Ormaechea, Olmo Ruiz
AU  - Werner, Diana
AU  - Erlebach, Lena
AU  - Bühler, Anika
AU  - Obermüller, Ulrike
AU  - Neher, Jonas J
AU  - Jucker, Mathias
AU  - Kronenberg-Versteeg, Deborah
TI  - Chimeric human organoid and mouse brain slice co-cultures to study microglial function.
JO  - Cell reports
VL  - 44
IS  - 12
SN  - 2211-1247
CY  - Maryland Heights, MO
PB  - Cell Press
M1  - DZNE-2025-01510
SP  - 116656
PY  - 2025
AB  - Studying the dynamic role of microglia in brain development and neurodegenerative diseases requires models that closely resemble the human brain environment. While human induced pluripotent stem cell (iPSC)-derived organoids (hORGs) effectively reproduce key neuronal and certain glial cell types, modeling human microglia in vitro remains challenging. Inspired by recent approaches demonstrating enhanced microglial maturation in hORGs transplanted into mouse brains, we develop a chimeric model by co-culturing hORGs with mouse brain slice cultures (mBSCs). This system reveals cross-species interactions associated with an earlier onset of cortical neuronal differentiation markers in the hORGs. Human iPSC-derived microglia, pre-differentiated in mBSCs, migrate into the hORGs and adopt ramified morphology. They remain viable for several months and respond to laser-induced injury, demonstrating long-term functionality. This in vitro model supports long-term study of human microglia in a brain-like environment, providing a platform for mechanistic studies and screening compounds that target microglial function.
KW  - Animals
KW  - Microglia: cytology
KW  - Microglia: metabolism
KW  - Humans
KW  - Organoids: cytology
KW  - Organoids: metabolism
KW  - Brain: cytology
KW  - Brain: metabolism
KW  - Coculture Techniques: methods
KW  - Induced Pluripotent Stem Cells: cytology
KW  - Induced Pluripotent Stem Cells: metabolism
KW  - Mice
KW  - Cell Differentiation
KW  - Neurons: cytology
KW  - Neurons: metabolism
KW  - CP: neuroscience (Other)
KW  - CP: stem cell research (Other)
KW  - cerebral organoids (Other)
KW  - chimeric in vitro model (Other)
KW  - human microglia (Other)
KW  - xenotransplantation (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:41385370
DO  - DOI:10.1016/j.celrep.2025.116656
UR  - https://pub.dzne.de/record/283103
ER  -