Human brain organoids respond to visual stimuli when transplanted into
adult rats

Date:
February 2, 2023
Source:
Cell Press
Summary:
Researchers show that brain organoids -- clumps of lab-grown
neurons - - can integrate with rat brains and respond to visual
stimulation like flashing lights.


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FULL STORY ==========================================================================
In a study publishing in the journal Cell Stem Cell on February 2,
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 senior author H. Isaac Chen, a
physician and Assistant Professor of Neurosurgery at the University of Pennsylvania. "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 Chen. "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 Chen. "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 Chen. "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."
* RELATED_TOPICS
o Health_&_Medicine
# Nervous_System # Stem_Cells # Brain_Tumor
o Mind_&_Brain
# Neuroscience # Brain_Injury # Brain-Computer_Interfaces
o Plants_&_Animals
# Mice # Biology # Biotechnology
* RELATED_TERMS
o Brain o Sensory_neuron o Brown_Rat o Retina o
Multiple_sclerosis o Social_cognition o Neural_network o
Optic_nerve

========================================================================== Story Source: Materials provided by Cell_Press. Note: Content may be
edited for style and length.


========================================================================== Journal Reference:
1. Dennis Jgamadze, James T. Lim, Zhijian Zhang, Paul M. Harary, James
Germi, Kobina Mensah-Brown, Christopher D. Adam, Ehsan Mirzakhalili,
Shikha Singh, Jiahe Ben Gu, Rachel Blue, Mehek Dedhia, Marissa Fu,
Fadi Jacob, Xuyu Qian, Kimberly Gagnon, Matthew Sergison, Oceane
Fruchet, Imon Rahaman, Huadong Wang, Fuqiang Xu, Rui Xiao, Diego
Contreras, John A.

Wolf, Hongjun Song, Guo-li Ming, Han-Chiao Isaac Chen. Structural
and functional integration of human forebrain organoids with the
injured adult rat visual system. Cell Stem Cell, 2023; 30 (2):
137 DOI: 10.1016/ j.stem.2023.01.004 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/02/230202112654.htm

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