Imagine if parts of the brain (mini-brains) that have been lost, damaged, or made sick could be grown back in the lab and then transplanted to give the person a new chance at life. Scientists at the University of California, San Diego, have made it more likely that this will happen.
When human cortical organoids, or “mini-brains,” were transplanted into mice, they not only connected to the vascular system of the host, but they also responded to pulses of light in the eyes of the test subjects in the same way as the rest of the brain tissue.
Researchers used a new imaging system to measure electrical activity in the organoid over the course of several months. This showed that the organoid had an integrated response to visual stimuli.
It is the first time that scientists have been able to validate functioning connections in a human brain organoid transplant in real-time. This is mostly because implants have gotten better and can now measure small signals from the mini-brains on a fine scale.
As the authors put it, “We believe that in the future this combination of stem cell and neurorecording technologies will be used to represent disease under physiological conditions at the level of neural circuits.”, combining organoids to “look at the prospective treatments based on a patient’s genetic background and assess their ability to restore specific missing, degraded, or injured brain regions,” the authors write.
The group of engineers and neuroscientists, led by neuro engineer Duygu Kuzum, made a new recording system that can measure mini-brains wave activity at both the macro and micro levels at the same time.
Microelectrodes made of graphene that are flexible and see-through can be implanted in certain parts of the brain. This finely tuned technology shows exactly when spikes in neural activity happen in both the transplanted organoid and the surrounding brain tissue. Less than a month after the transplant, researchers found that their human organoids had made functional synaptic connections with the rest of the mouse visual cortex. After two months, the foreign tissue had become even more a part of the host’s brain.
Previous research, some of which was done at UCSD by the same authors, has shown that human mini-brains can connect to blood vessels that bring oxygen and nutrients to the brain. The neurons also start to grow up and arrange themselves.
In 2019, for example, scientists grew pluripotent stem cells into a blob the size of a pea that was made up of two million organized neurons. This blob looked around to find connections with nearby cells.
Pluripotent stem cells also make up the building blocks of organoids of the human brain. They can turn into many different kinds of tissues and organs, but only if they are surrounded by the right mix of molecules. Scientists are still trying to figure out how that mixture works because it is so complicated and depends on very specific timing.
In 2021, a brain organoid started to grow the beginnings of eye structures. However, it is still a long way from being possible for a lab-grown brain to have functional “sight.”
On the other hand, it might be more realistic to try to implant human brain tissue grown from stem cells into a fully developed visual cortex. This has been done before with rodents, but it has been harder to figure out if the foreign graft is actively getting functional input from the rest of the brain.
Conventional metal electrodes don’t give a clear view of the brain, so scientists have to take them off to see the sensory cortex. This can mess up the success of a tissue graft.
This problem can be fixed by using electrodes that are clear. Under a microscope, UCSD researchers used fluorescent imaging to show that pulses of light can stimulate human organoids that have been transplanted into the brain of a mouse.
We envision a future where stem cells and neurorecording technologies are utilized together to create physiological illness models and put hypotheses about how to treat such diseases to the test using organoids derived from the brains of individual patients., and test the ability of organoids to repair specific brain regions that have been lost, damaged, or degenerated,” says Kuzum.
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