Human cerebral organoids establish subcortical projections in the mouse brain after transplantation.
Mol Psychiatry
; 26(7): 2964-2976, 2021 07.
Article
in En
| MEDLINE
| ID: mdl-33051604
ABSTRACT
Numerous studies have used human pluripotent stem cell-derived cerebral organoids to elucidate the mystery of human brain development and model neurological diseases in vitro, but the potential for grafted organoid-based therapy in vivo remains unknown. Here, we optimized a culturing protocol capable of efficiently generating small human cerebral organoids. After transplantation into the mouse medial prefrontal cortex, the grafted human cerebral organoids survived and extended projections over 4.5 mm in length to basal brain regions within 1 month. The transplanted cerebral organoids generated human glutamatergic neurons that acquired electrophysiological maturity in the mouse brain. Importantly, the grafted human cerebral organoids functionally integrated into pre-existing neural circuits by forming bidirectional synaptic connections with the mouse host neurons. Furthermore, compared to control mice, the mice transplanted with cerebral organoids showed an increase in freezing time in response to auditory conditioned stimuli, suggesting the potentiation of the startle fear response. Our study showed that subcortical projections can be established by microtransplantation and may provide crucial insights into the therapeutic potential of human cerebral organoids for neurological diseases.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pluripotent Stem Cells
/
Induced Pluripotent Stem Cells
Type of study:
Guideline
Limits:
Animals
/
Humans
Language:
En
Journal:
Mol Psychiatry
Journal subject:
BIOLOGIA MOLECULAR
/
PSIQUIATRIA
Year:
2021
Type:
Article
Affiliation country:
China