@article{3feea61bb23a40bd8376550c27f4efe9,
title = "Midbrain-like Organoids from Human Pluripotent Stem Cells Contain Functional Dopaminergic and Neuromelanin-Producing Neurons",
abstract = "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.",
author = "Junghyun Jo and Yixin Xiao and Sun, {Alfred Xuyang} and Engin Cukuroglu and Tran, {Hoang Dai} and Jonathan G{\"o}ke and Tan, {Zi Ying} and Saw, {Tzuen Yih} and Tan, {Cheng Peow} and Hidayat Lokman and Younghwan Lee and Donghoon Kim and Ko, {Han Seok} and Kim, {Seong Oh} and Park, {Jae Hyeon} and Cho, {Nam Joon} and Hyde, {Thomas M.} and Kleinman, {Joel E.} and Shin, {Joo Heon} and Weinberger, {Daniel R.} and Tan, {Eng King} and Je, {Hyunsoo Shawn} and Ng, {Huck Hui}",
note = "Funding Information: We thank K.L. Lim and C. Chou for generously sharing reagents. We thank K.A. Gonzales, Y.S. Chan, and Y.S. Lim for assistance with experiments and intellectual discussion. We also thank O. Pletnikova and J. Troncoso for generously providing postmortem midbrain tissue samples. This work was supported by the Singapore Ministry of Education Academic Research Fund (MOE2012-T2-1-021), an Agency for Science, Technology and Research (A ∗ STAR) Translational Collaborative Research Partnership Grant (TCRP, 13/1/96/688), a Duke-NUS Signature Research Program Block Grant (to H.S.J.), a National Medical Research Council Translational and Clinical Flagship grant (E.K.T. and H.H.N.), and A∗STAR (H.H.N.). This work was also supported by grants from the NIH (NS082205 and NS38377) and the Maryland Stem Cell Research Foundation (RFA-MD-13-2). The authors acknowledge the joint participation by the Adrienne Helis Malvin Medical Research Foundation and the Diana Helis Henry Medical Research Foundation through its direct engagement in the continuous active conduct of medical research in conjunction with The Johns Hopkins Hospital, the Johns Hopkins University School of Medicine, the Foundation's Parkinson's Disease Program H-1, H-2013. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = aug,
day = "4",
doi = "10.1016/j.stem.2016.07.005",
language = "English (US)",
volume = "19",
pages = "248--257",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "2",
}