Creating Mini Brains from Stem Cells Gets Automated

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Scientists published a new study published in Scientific Reports that showcases a new platform that automates the growth of brain organoids, offering neuroscientists research improved flexibility and quality control.

“The increasing demands for long-term experiments, reproducibility, parallelization, and longitudinal analysis drive cell culture toward automation,” the researchers at the University of California at Santa Cruz wrote. “This study showcases an automated, microfluidic solution for the growth and maintenance of organoids capable of existing in conjunction with other control and sensing devices over the Internet of Things, magnifying the ability to capitalize on precision robotics for automated experimentation.”

One of the greatest challenges in neuroscience is having living human brains in which to conduct research. Neuroscientists study the human brain, the central nervous system, as well as neurological and psychiatric disorders to discover potential treatments and cures. Brain organoids, 3D brain-like structures consisting of human stem cells, offer a way to study brain diseases and disorders and test potential medication and treatments.

The history of brain organoids is fairly recent. In 2006 scientists Shinya Yamanaka, a recipient of the 2012 Nobel Prize in Physiology or Medicine, and Kazutoshi Takahashi were the first to create induced pluripotent stem cells (iPSCs). The duo created stem cells in a lab by applying four transcription factors to the mature skin cells of mice. Transcription factors are the molecules that play a role in regulating gene expression. Transcription factors are typically proteins, but they can be made up of non-coding RNA as well. Yamanaka and others demonstrated that this technique worked for human skin cells in 2007.

The first three-dimensional cluster of cells or organoids, including brain organoids, emerged in 2009 using iPSCs. A decade later in 2019, a payload of a hundred stem cell-derived human brain organoids was sent to the International Space Station by University of California at San Diego researchers in partnership with Space Tango to advance the understanding of neurological diseases and assess microgravity’s impact on neural development.

“We developed an automated, microfluidic cell culture platform to optimize 3D organoid growth, the “Autoculture” platform,” wrote the researchers.

The Autoculture platform consists of a microfluidic organoid chip made of polydimethylsiloxane (PDMS) with 24 wells that can be individually controlled, a control interface, refrigerated reagent reservoirs, syringe pump, distribution valves, collection reservoirs, and an incubator. PDMS is a type of silicone that is well-suited for studying neural stem cell behavior given its flexible, oxidation-resistant, and heat-tolerant properties. Autoculture has an Internet of Things (IoT) integration with the Amazon Web Services (AWS) cloud. It can be operated remotely using to start, monitor, stop, pause, edit, and design experiments on demand.

“By reducing concentration fluctuations in the cell culture media through automated feeding, the cultures may experience greater homeostasis,” the researchers reported.

The researchers compared the stress levels of organoids produced by Autoculture versus traditional suspension culture environment. According to the scientists, their platform produces organoids with fewer stress levels.

“Reducing stress levels in cerebral organoid models is crucial to achieving physiological relevance,” the researchers wrote. “As measured by reduced glycolytic enzyme expression, the environment of the Autoculture platform results in reduced-stress organoids compared to traditional suspension culture conditions.”

This proof-of-concept of automating the production of brain organoids paves the way for precision robotics for accelerating neuroscience research and discoveries in the future.

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