Three-dimensional microfluidics with dynamic fluidic perturbation promotes viability and uniformity of human cerebral organoids

被引：7

作者：

Abdulla, Aynur ^{[1
,2
,3
]}

Chen, Shujin ^{[4
]}

Chen, Zhecong ^{[1
,2
]}

Wang, Yukun ^{[5
]}

Yan, Haoni ^{[1
,2
,3
]}

Chen, Rui ^{[3
]}

Ahmad, Khan Zara ^{[3
]}

Liu, Kun ^{[6
]}

Yan, Chonghuai ^{[4
]}

He, Jie ^{[7
]}

Jiang, Lai ^{[1
,2
]}

Ding, Xianting ^{[1
,2
,3
]}

机构：

[1] Shanghai Jiao Tong Univ, Xinhua Hosp, Sch Med, Dept Anesthesiol, Shanghai, Peoples R China

[2] Shanghai Jiao Tong Univ, Xinhua Hosp, Sch Med, Surg Intens Care Unit, Shanghai, Peoples R China

[3] Shanghai Jiao Tong Univ, Inst Personalized Med, Sch Biomed Engn, State Key Lab Oncogenes & Related Genes, Shanghai, Peoples R China

[4] Shanghai Jiao Tong Univ, Xinhua Hosp, Sch Med, Shanghai Key Lab Childrens Environm Hlth,Minist Ed, Shanghai, Peoples R China

[5] Tech Univ Munich, Sch Engn & Design, Munich, Germany

[6] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Sch Med, Dept Cardiol, Shanghai, Peoples R China

[7] Inst Neurosci, CAS Ctr Excellence Brain Sci & Intelligence Techno, State Key Lab Neurosci, Shanghai, Peoples R China

来源：

BIOSENSORS & BIOELECTRONICS | 2023年 / 240卷

基金：

国家重点研发计划;

关键词：

Cerebral organoids; Organ on chip; Dynamic culturing; BRAIN ORGANOIDS; GENERATION;

D O I：

10.1016/j.bios.2023.115635

中图分类号：

Q6 [生物物理学];

学科分类号：

071011 ;

摘要：

Human cerebral organoids (COs), generated from stem cells, are emerging animal alternatives for understanding brain development and neurodegeneration diseases. Long-term growth of COs is currently hindered by the limitation of efficient oxygen infiltration and continuous nutrient supply, leading to general inner hypoxia and cell death at the core region of the organoids. Here, we developed a three-dimensional (3D) microfluidic platform with dynamic fluidic perturbation and oxygen supply. We demonstrated COs cultured in the 3D microfluidic system grew continuously for over 50 days without cell death at the core region. Increased cell proliferation and enhanced cell differentiation were also observed and verified with immunofluorescence staining, proteomics and metabolomics. Time-lapse proteomics from 7 consecutive acquisitions between day 4 and day 30 identified 546 proteins differently expressed accompanying COs growth, which were mainly relevant to nervous system development, in utero embryonic development, brain development and neuron migration. Our 3D microfluidic platform provides potential utility for culturing high-homogeneous human organoids.

引用

页数：9

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