The
researchers show that brain organoids—clumps of lab-grown neurons—can
integrate with rat brains and respond to visual stimulation like
flashing lights.
Decades
of research has shown that we can transplant individual human and
rodent neurons into rodent brains, and, more recently, it has been
demonstrated that human brain organoids can integrate with developing
rodent brains. However, whether these organoid grafts can functionally
integrate with the visual system of injured adult brains has yet to be
explored.
“We
focused on not just transplanting individual cells, but actually
transplanting tissue,” says the senior author. “Brain organoids have
architecture; they have structure that resembles the brain. We were able
to look at individual neurons within this structure to gain a deeper
understanding of the integration of transplanted organoids.”
The
researchers cultivated human stem cell-derived neurons in the lab for
around 80 days before grafting them into the brains of adult rats that
had sustained injuries to their visual cortex. Within three months, the
grafted organoids had integrated with their host’s brain: becoming
vascularized, growing in size and number, sending out neuronal
projections, and forming synapses with the host’s neurons.
The
team made use of fluorescent-tagged viruses that hop along synapses,
from neuron to neuron, to detect and trace physical connections between
the organoid and brain cells of the host rat. “By injecting one of these
viral tracers into the eye of the animal, we were able to trace the
neuronal connections downstream from the retina,” says the author. “The
tracer got all the way to the organoid.”
Next,
the researchers used electrode probes to measure the activity of
individual neurons within the organoid when the animals were exposed to
flashing lights and alternating white and black bars. “We saw that a
good number of neurons within the organoid responded to specific
orientations of light, which gives us evidence that these organoid
neurons were able to not just integrate with the visual system, but they
were able to adopt very specific functions of the visual cortex.”
The
team was surprised by the degree to which the organoids were able to
integrate within only three months. “We were not expecting to see this
degree of functional integration so early,” says the author. “There have
been other studies looking at transplantation of individual cells that
show that even 9 or 10 months after you transplant human neurons into a
rodent, they're still not completely mature.”
“Neural
tissues have the potential to rebuild areas of the injured brain,” says
the author. “We haven't worked everything out, but this is a very solid
first step. Now, we want to understand how organoids could be used in
other areas of the cortex, not just the visual cortex, and we want to
understand the rules that guide how organoid neurons integrate with the
brain so that we can better control that process and make it happen
faster.”
https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00004-8
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fstructural-and_11&filter=22