Journal
CELL STEM CELL
Volume 19, Issue 2, Pages 248-257Publisher
CELL PRESS
DOI: 10.1016/j.stem.2016.07.005
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Funding
- Singapore Ministry of Education Academic Research Fund [MOE2012-T2-1-021]
- Agency for Science, Technology and Research (A*STAR) Translational Collaborative Research Partnership Grant (TCRP) [13/1/96/688]
- Duke-NUS Signature Research Program Block Grant
- National Medical Research Council Translational and Clinical Flagship grant
- A*STAR
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Recent advances in 3D culture systems have led to the generation of brain organoids that resemble different human brain regions; however, a 3D organoid model of the midbrain containing functional midbrain dopaminergic (mDA) neurons has not been reported. We developed a method to differentiate human pluripotent stem cells into a large multicellular organoid-like structure that contains distinct layers of neuronal cells expressing characteristic markers of human midbrain. Importantly, we detected electrically active and functionally mature mDA neurons and dopamine production in our 3D midbrain-like organoids (MLOs). In contrast to human mDA neurons generated using 2D methods or MLOs generated from mouse embryonic stem cells, our human MLOs produced neuromelanin-like granules that were structurally similar to those isolated from human substantia nigra tissues. Thus our MLOs bearing features of the human midbrain may provide a tractable in vitro system to study the human midbrain and its related diseases.
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