Many ethical, as well as supply issues, surround the use of human brain tissue in research, because of this stem cells are used to develop mini-brains or ‘organoids’, a pea-sized model of the human brain, in a lab dish. By using a culture medium mimicking the environment of brain development, the stem cells self-organize into a 3D structure resembling the developing human brain. However, only a handful of studies have successfully used 3D cell culture techniques to achieve this. Now, a study from researchers at the University of California, San Diego engineers miniature brains from stem cells that spontaneously develop functional neural networks. The team states despite being a million times smaller than human brains, their lab-grown brains are the first to produce brainwaves resembling those of preterm babies. The opensource study is published in the journal Cell Stem Cell.

Previous studies show research in early brain development has been slow, in part due to the fact it is difficult to obtain fetal-tissue samples for analysis and to examine a fetus in utero. Therefore, there is much interest in the development of brain ‘organoids’, which, when grown in 3D cultures, can develop some of the complex structures seen in the brains of animals or humans. However, there is no evidence these organoids develop essential complex and functional neural network activity that appears when neurons are mature and become interconnected. The current study develops lab-grown brains capable of forming intricate networks of neurons producing strong brainwaves. 

The current study optimizes the 3D cell culture medium to enable brain organoids to become more mature than previous models. Hundreds of organoids were grown for 10 months, using multi-electrode arrays to monitor their neural activities. Results show bursts of brainwaves were detected from organoids at about two months. Data findings show the signals were sparse and had the same frequency or pattern seen in very immature human brains. 

Results show as the organoids continue to grow, they produce brainwaves at different frequencies, with the signals appearing more regularly, suggesting the development of neural networks over time. The lab explains to compare the brainwave patterns of organoids with those of human brains early in development, they used an algorithm modeling brainwaves recorded from 39 premature babies between six and nine-and-a-half months old. They observed the algorithm was able to predict how many weeks the organoids have developed in culture, which suggests these organoids and the human brain share a similar growth trajectory. They stress it’s highly unlikely their organoids are self-aware.

The team surmises they have detected functional brainwaves from mini-brains they grew in 3D cell culture medium. For the future, the researchers state findings suggest these organoids are suitable for the investigation into neural network formation at the early and late stages of human brain development.

Source: University of California, San Diego

 

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