January/February 2019^ DISCOVER^69
CLOCKWISE FROM TOP: ALYSSON MUOTRI (2); SALK INSTITUTE; A. MANSOUR ET AL./NATURE BIOTECHNOLOGY/APRIL 16, 2018
Green fluorescent
protein + human
embryonic
stem cellsHuman cerebral
organoids (“mini-
brains”) grown
in cultureOrganoid
grafted into
cavity made in
mouse brainBlood vessels and
neurons grow and
connect to implanted
organoidOut of the Dish and Into the Mouse
Neuroscientists have implanted human brain organoids into mice — the first time
they’ve done so in any animal. And the implants are taking.
In a paper published in April in Nature Biotechnology, researchers describe how
the mini-brains, grafted into adult mice, quickly incorporated into their hosts. Within
seven days, blood vessels from the host mouse had woven throughout the organoid.
After 90 days, axons — the nerve fibers that carry neurons’ outgoing messages —
had connected with host neurons.
The move is an important step forward in regenerative medicine. If cerebral
organoids can survive in mice, then something similar in humans becomes more
feasible. And if it works in humans, we might be able to repair brain damage. Still,
grafting a rudimentary human brain into an animal crosses into tricky consciousness
territory. Critics contend that we need to establish ethical guidelines before
researchers can scale things up to work in humans.organoids.) His lab focused on our
NOVA1 gene, a so-called master
regulator gene that inuences the
expression of hundreds of others.
When the team swapped in the
Neanderthal equivalent of NOVA1,
the organoids’ neural structure
developed unusually, mirroring
some of the developmental
differences seen in people
with autism.
But Muotri knows this isn’t
even close to revealing how
Neanderthals thought. They’re
testing only one genetic mutation
at a time, so they can’t know
how multiple mutations would
interact. The research has not yet
reached the stage where it would
be possible to test for differences in
function. Then there’s the issue of
how simplistic the model is: It can
approximate development “that is
similar to a newborn baby,” Muotri
says, but “it is dificult to make
conclusions about the adult brain.”
Limitations aside, he believes this
work will eventually help us igure
out how our brains evolved, and
could even pinpoint the origins of
brain diseases and disorders such as
schizophrenia and autism.Brain organoids grown from two
closely related species, Homo sapiens
(above) and Neanderthals (below)
differ noticeably in shape even during
the early phases of the research
project. A single gene switch in the
Neanderthal mini-brains prompted
significant developmental changes.A network of neurons (small
points in red) is visible within
human organoid tissue (green)
that has been grafted into a
mouse brain (larger red area).Putting a Human Brain Into a Mouse