Midbrain-like organoids from human pluripotent stem cells contain functional dopaminergic and neuromelanin producing neurons
By J. Jo, Yixin Xiao, A. Sun, Engin Cukuroglu, Hoang-Dai Tran, Jonathan Göke, Zi-Ying Tan, T. Y. Saw, Cheng-Peow Tan, Hidayat Lokman and 13 more. Cell Stem Cell, 2016
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SUMMARY Recent advances in three dimensional (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.
Subfields: Developmental Neuroscience, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/0b55bb029426457a60e5eaef45bf73563a0bfe62
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Citations in the corpus
- Brain organoids: advances, applications and challenges (2019, background): “…are hPSC-derived organoids that self-assemble to form an organized architecture, composed of progenitor, neuronal and glial cell types, resembling the fetal human brain (Jo et al., 2016; Kadoshima et al., 2013; Lancaster et al., 2013; Mariani et al., 2015; Pasca et al., 2015; Qian et al., 2016).”