한빛사논문
Ann-Na Cho1,12, Yoonhee Jin1,12, Yeonjoo An1,12, Jin Kim1, Yi Sun Choi1, Jung Seung Lee1, Junghoon Kim1, Won-Young Choi2, Dong-Jun Koo3, Weonjin Yu4, Gyeong-Eon Chang1, Dong-Yoon Kim3, Sung-Hyun Jo5, Jihun Kim6, Sung-Yon Kim3,7, Yun-Gon Kim5, Ju Young Kim8, Nakwon Choi9, Eunji Cheong1, Young-Joon Kim2, Hyunsoo Shawn Je4, Hoon-Chul Kang6 & Seung-Woo Cho1,10,11,*
1Department of Biotechnology, Yonsei University, Seoul, Republic of Korea. 2Department of Biochemistry, Yonsei University, Seoul, Republic of Korea. 3Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Republic of Korea. 4Signature Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore, Singapore. 5Department of Chemical Engineering, Soongsil University, Seoul, Republic of Korea. 6Division of Pediatric Neurology, Department of Pediatrics, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. 7Department of Chemistry, Seoul National University, Seoul, Republic of Korea. 8Department of Advanced Materials Engineering, Kangwon National University, Samcheok, Republic of Korea. 9Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea. 10Center for Nanomedicine, Institute for Basic science (IBS), Seoul, Republic of Korea. 11Graduate Program of Nano Biomedical Engineering (NanoBME), Advanced Science Institute, Yonsei University, Seoul, Republic of Korea. 12These authors contributed equally: Ann-Na Cho, Yoonhee Jin, Yeonjoo An.
*Corresponding author.
Abstract
Brain organoids derived from human pluripotent stem cells provide a highly valuable in vitro model to recapitulate human brain development and neurological diseases. However, the current systems for brain organoid culture require further improvement for the reliable production of high-quality organoids. Here, we demonstrate two engineering elements to improve human brain organoid culture, (1) a human brain extracellular matrix to provide brain-specific cues and (2) a microfluidic device with periodic flow to improve the survival and reduce the variability of organoids. A three-dimensional culture modified with brain extracellular matrix significantly enhanced neurogenesis in developing brain organoids from human induced pluripotent stem cells. Cortical layer development, volumetric augmentation, and electrophysiological function of human brain organoids were further improved in a reproducible manner by dynamic culture in microfluidic chamber devices. Our engineering concept of reconstituting brain-mimetic microenvironments facilitates the development of a reliable culture platform for brain organoids, enabling effective modeling and drug development for human brain diseases.
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