One-Stop Microfluidic Assembly of Human Brain Organoids To Model Prenatal Cannabis Exposure
| Autor: | Feng Guo, Daniel J Havert, Ken Mackie, Zhuhao Wu, Zhiyi Gong, John M. Beggs, Zheng Ao, Hongwei Cai |
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| Rok vydání: | 2020 |
| Předmět: |
Cannabinoid receptor
Neurite medicine.medical_treatment Biology 010402 general chemistry Models Biological 01 natural sciences Analytical Chemistry Pregnancy Lab-On-A-Chip Devices Cannabinoid receptor type 1 Organoid medicine Humans Hypoxia Receptor Electrodes Cells Cultured Embryonic Stem Cells Cannabis Chemistry 010401 analytical chemistry Brain Human brain Embryonic stem cell 0104 chemical sciences Cell biology Organoids medicine.anatomical_structure Prenatal Exposure Delayed Effects Female Cannabinoid |
| Zdroj: | Analytical Chemistry. 92:4630-4638 |
| ISSN: | 1520-6882 0003-2700 |
| Popis: | Prenatal cannabis exposure (PCE) influences human brain development, but it is challenging to model PCE using animals and current cell culture techniques. Here, we developed a one-stop microfluidic platform to assemble and culture human cerebral organoids from human embryonic stem cells (hESC) to investigate the effect of PCE on early human brain development. By incorporating perfusable culture chambers, air-liquid interface, and one-stop protocol, this microfluidic platform can simplify the fabrication procedure, and produce a large number of organoids (169 organoids per 3.5 cm x 3.5 cm device area) without fusion, as compared with conventional fabrication methods. These one-stop microfluidic assembled cerebral organoids not only recapitulate early human brain structure, biology, and electrophysiology but also have minimal size variation and hypoxia. Under on-chip exposure to the psychoactive cannabinoid, delta-9-tetrahydrocannabinol (THC), cerebral organoids exhibited reduced neuronal maturation, downregulation of cannabinoid receptor type 1 (CB1) receptors, and impaired neurite outgrowth. Moreover, transient on-chip THC treatment also decreased spontaneous firing in microfluidic assembled brain organoids. This one-stop microfluidic technique enables a simple, scalable, and repeatable organoid culture method that can be used not only for human brain organoids, but also for many other human organoids including liver, kidney, retina, and tumor organoids. This technology could be widely used in modeling brain and other organ development, developmental disorders, developmental pharmacology and toxicology, and drug screening. |
| Databáze: | OpenAIRE |
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