Microfluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids

被引：242

作者：

Cho, Ann-Na ^{[1
]}

Jin, Yoonhee ^{[1
]}

An, Yeonjoo ^{[1
]}

Kim, Jin ^{[1
]}

Choi, Yi Sun ^{[1
]}

Lee, Jung Seung ^{[1
]}

Kim, Junghoon ^{[1
]}

Choi, Won-Young ^{[2
]}

Koo, Dong-Jun ^{[3
]}

Yu, Weonjin ^{[4
]}

Chang, Gyeong-Eon ^{[1
]}

Kim, Dong-Yoon ^{[3
]}

Jo, Sung-Hyun ^{[5
]}

Kim, Jihun ^{[6
]}

Kim, Sung-Yon ^{[3
,7
]}

Kim, Yun-Gon ^{[5
]}

Kim, Ju Young ^{[8
]}

Choi, Nakwon ^{[9
]}

Cheong, Eunji ^{[1
]}

Kim, Young-Joon ^{[2
]}

Je, Hyunsoo Shawn ^{[4
]}

Kang, Hoon-Chul ^{[6
]}

Cho, Seung-Woo ^{[1
,10
,11
]}

机构：

[1] Yonsei Univ, Dept Biotechnol, Seoul, South Korea

[2] Yonsei Univ, Dept Biochem, Seoul, South Korea

[3] Seoul Natl Univ, Inst Mol Biol & Genet, Seoul, South Korea

[4] Duke NUS Med Sch, Signat Program Neurosci & Behav Disorders, Singapore, Singapore

[5] Soongsil Univ, Dept Chem Engn, Seoul, South Korea

[6] Yonsei Univ, Severance Childrens Hosp, Dept Pediat, Div Pediat Neurol,Coll Med, Seoul, South Korea

[7] Seoul Natl Univ, Dept Chem, Seoul, South Korea

[8] Kangwon Natl Univ, Dept Adv Mat Engn, Samcheok, South Korea

[9] Korea Inst Sci & Technol KIST, Brain Sci Inst, Seoul, South Korea

[10] Inst Basic Sci IBS, Ctr Nanomed, Seoul, South Korea

[11] Yonsei Univ, Adv Sci Inst, Grad Program Nano Biomed Engn NanoBME, Seoul, South Korea

来源：

NATURE COMMUNICATIONS | 2021年 / 12卷 / 01期

基金：

新加坡国家研究基金会; 英国医学研究理事会;

关键词：

PLURIPOTENT STEM-CELLS; ON-A-CHIP; CEREBRAL ORGANOIDS; SELF-ORGANIZATION; NEURONAL MIGRATION; WHOLE-BRAIN; IN-VITRO; MODEL; DIFFERENTIATION; DYNAMICS;

D O I：

10.1038/s41467-021-24775-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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. Brain organoids derived from human pluripotent stem cells can model human brain development and disease, though current culture systems fail to ensure reliable production of high-quality organoids. Here the authors combine human brain extracellular matrix and culture in a microfluidic device to promote structural and functional maturation of human brain organoids.

引用

页数：23

共 88 条

[1] A high-throughput screening for mammalian cell death effectors identifies the mitochondrial phosphate carrier as a regulator of cytochrome c release [J].