Human 'Mini-Brains' Implanted in Mice Respond to Light in Scientific First
rael-science
Human 'Mini-Brains' Implanted in Mice Respond to Light in Scientific First
The researchers observed electrical activity in the electrode channels above the organoids, showing a reaction to the stimulus. (David Baillot/UC San Diego)Imagine
if lost, degenerated, or diseased parts of the brain could be regrown
in the lab and transplanted for a new lease on life. Scientists at the
University of California San Diego have gotten us closer to that
reality.
Human cortical organoids (or 'mini-brains')
transplanted into mice not only connected with the host's vascular
system, they reacted to pulses of light shone into the test subjects'
eyes in similar ways to the surrounding brain tissue.
Over
the course of several months, researchers used an innovative imaging
system to measure electrical activity in the organoid that indicated an
integrated response to visual stimuli.
It's
the first time scientists have been able to confirm functional
connections in a transplanted human brain organoid in real time, largely
thanks to improvements in implants capable of measuring subtle
neurological signalling on a fine scale.
"We envision that, further along the road, this combination of stem cell and
neurorecording technologies will be used for modeling disease under
physiological conditions at a level of neuronal circuits, examination of
candidate treatments on patient-specific genetic background, and
evaluation of organoids' potential to restore specific lost,
degenerated, or damaged brain regions upon integration," the authors write.
The
team of engineers and neuroscientists, led by neuroengineer Duygu
Kuzum, developed their new recording system to measure brain wave
activity at both a macro and micro level at the same time.
The setup uses flexible and transparent microelectrodes made from graphene that
can be implanted into certain parts of the brain. This highly-tuned
tech accurately displays spikes in neural activity from both the
transplanted organoid and surrounding brain tissue as they occur.
Less
than a month after transplantation, researchers found their human
organoids had formed functional synaptic connections with the rest of
the mouse visual cortex.
Two months later, the foreign tissue had integrated with the host's brains even further.
Previous studies, some conducted by the same authors at UCSD,
have shown that human mini-brains implanted into mice can connect to
blood vessels supplying oxygen and nutrients. The neurons also start to
mature and self-organize.
In 2019, for instance, scientists grew pluripotent stem cells into a pea-sized blob of two million organized neurons that probed its surroundings for neighborly connections.
Pluripotent
stem cells also form the foundation of human brain organoids. They have
the potential to differentiate into a wide variety of tissues and
organs, but only if they are bathed in the right cocktail of molecules.
But that mixture is incredibly complex and based on very specific
timing, which scientists are still working out.
In 2021, headlines were made when a brain organoid started to develop rudimentary eye structures, and yet the feasibility of achieving functional 'sight' in a lab-grown brain is still a long way off.
Implanting
a human brain tissue grown from stem cells into a developed visual
cortex, on the other hand, could be a more realistic goal. Studies have achieved this before in rodents, but whether the foreign graft is actively receiving functional input from the rest of the brain has been harder to determine.
Conventional
metal electrodes do not give a clear field of view to the brain, which
means scientists have to remove the electrodes to properly see the
sensory cortex, and this can mess with the success of a tissue graft.
Transparent
electrodes help solve that problem. Using a fluorescent imaging
technique under the microscope, researchers at UCSD have shown that
pulses of light can stimulate transplanted human organoids within a
mouse brain.
"We
envision that, further along the road, this combination of stem cells
and neurorecording technologies will be used for modeling disease under
physiological conditions; examining candidate treatments on
patient-specific organoids; and evaluating organoids' potential to
restore specific lost, degenerated or damaged brain regions," says Kuzum.
The study was published in Nature Communications.
