Human mini-brains implanted in mice react to the light seen by the animals

PFor the first time, a miniature human brain grown from stem cells and implanted into living mice reacted to what the latter saw. Scientists were able to observe these reactions in real time using special graphene electrodes.

Caption: Tiny human brain “organoids” in a lab dish. (David Baillot/UC San Diego)

In recent years, scientists have found a way to revert mature skin cells to an immature state that can then transform into almost any other type of cell in the body. These induced pluripotent stem cells can be used in the laboratory to make small but functional versions of organs called organoids.

Because they are a more natural three-dimensional representation of reality, organelles can be used to model development, disease, and drug responses more accurately than flat cultures of cells in a box. Over the years, scientists have managed to grow miniature versions of the brain, heart, lungs, liver, kidneys, stomachs, eyes, pancreas, and even blood vessels and hair follicles. .

Last October, a Stanford University team implanted human brain organelles into rats for the first time and found that human cells were communicating with rat neurons. In this new study (link below), scientists at the University of California have continued this work by showing that human brain organelles implanted in mice can respond to stimuli.

According to the study: generation of induced human pluripotent stem cells (hiPSCs) from skin fibroblasts; culture of hiPSC-derived organelles for implantation into mouse cortex. (Madison N. Wilson et al./Nature Communications)

Previously, this phenomenon was difficult to observe, because the brain activity in question lasts only a few milliseconds, and current technology has difficulty capturing it. The UC San Diego team therefore combined two experimental techniques to image brain cells.

First, he placed an array of transparent graphene electrodes on the transplanted organelles. These devices allowed the team to record neural electrical activity in both human brain cells and surrounding mouse brain tissue. Next, they used two-photon excitation microscopy to visualize the brains and found that the mice’s blood vessels had become organelles, supplying them with oxygen and nutrients.

Graphene electrodes allow scientists to measure the electrical activity of human brain organelles and surrounding brain tissue in mice. (David Baillot/UC San Diego)

Three weeks after the implantation, the researchers conducted experiments during which they projected white light in front of the mice and observed the reactions of different brain cells. Sure enough, the graphene electrodes showed clear signs of electrical stimulation emanating from the visual cortex. This proved that the human organelles formed synaptic connections with the surrounding mouse brain tissue. Over 11 weeks of experiments, the team showed that the implants became increasingly functionally integrated with the host.

According to Madison Wilson, the first author of the study:

No other study has been able to simultaneously record optically and electrically. Our experiments show that visual stimuli evoke electrophysiological responses in organelles that correspond to responses from the surrounding cortex.

In future work, the team plans to use this technique to model the progression of neurological diseases, which could eventually help uncover potential new treatments.

A study published in the journal Nature Communications: Multimodal monitoring of human cortical organelles implanted in mice reveals functional connectivity with visual cortex and presented at the University of California, San Diego website: Human brain organelles implanted in mouse cortex respond to visual stimuli for the first time.