Human cerebral organoids establish subcortical projections in the mouse brain after transplantation
| Autor: | Shi-Bo Xu, Xin Dong, Shuijin He, Yufeng Pan, Yuejun Chen, Xiao-Yan Tang, Min Xu, Yan Liu, Xin Chen, Mengdan Tao, Kai-Heng Fang |
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| Rok vydání: | 2020 |
| Předmět: |
Pluripotent Stem Cells
0301 basic medicine Cell biology Induced Pluripotent Stem Cells Stem cells Biology Article Mice 03 medical and health sciences Cellular and Molecular Neuroscience Glutamatergic 0302 clinical medicine Organoid medicine Biological neural network Animals Humans Prefrontal cortex Molecular Biology Neurons Brain Cell Differentiation Long-term potentiation Human brain Microtransplantation Electrophysiological Phenomena Organoids Transplantation Psychiatry and Mental health 030104 developmental biology medicine.anatomical_structure Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Molecular Psychiatry |
| ISSN: | 1476-5578 1359-4184 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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