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

Aynur Abdulla; Shujin Chen; Zhecong Chen; Yukun Wang; Haoni Yan; Rui Chen; Khan Zara Ahmad; Kun Liu; Chonghuai Yan; Jie He; Lai Jiang; Xianting Ding

doi:10.1016/j.bios.2023.115635

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

Biosens Bioelectron. 2023 Nov 15:240:115635. doi: 10.1016/j.bios.2023.115635. Epub 2023 Aug 25.

Authors

Aynur Abdulla¹, Shujin Chen², Zhecong Chen³, Yukun Wang⁴, Haoni Yan¹, Rui Chen⁵, Khan Zara Ahmad⁵, Kun Liu⁶, Chonghuai Yan², Jie He⁷, Lai Jiang⁸, Xianting Ding⁹

Affiliations

¹ Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
² Ministry of Education, Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
³ Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁴ School of Engineering and Design, Technical University of Munich, Munich, Germany.
⁵ State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
⁶ Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁷ Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, China. Electronic address: jiehe@ion.ac.cn.
⁸ Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: jianglai@xinhuamed.com.cn.
⁹ Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China. Electronic address: dingxianting@sjtu.edu.cn.

PMID: 37651948
DOI: 10.1016/j.bios.2023.115635

Abstract

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.

Keywords: Cerebral organoids; Dynamic culturing; Organ on chip.

MeSH terms

Animals
Biosensing Techniques*
Cell Death
Female
Humans
Microfluidics*
Organoids
Oxygen
Pregnancy

Substances

Oxygen