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▎WuXi AppTec's content team edited
the emergence of induced pluripotent stem cells, which has allowed scientists to make rapid progress in the field of stem cells and developmental biology, and one of the most promising applications is organoids
.
With the differentiation ability of stem cells, researchers can make stem cells form aggregates under 3D conditions, and then orient them towards an organ and tissue
.
These cells eventually self-assemble into miniature, organ-like clumps that mimic livers, kidneys, or brains
.
Brain organoids make neuroscience research more convenient, and scientists can directly manipulate neurons of interest in petri dishes to find the neural mechanisms behind them or potential drug targets
.
Image source: 123RF
However, the brain organoids in the petri dish are not perfect, and the neural tissue is always difficult to fully mature and differentiate correctly, so it will also lack some connections in the real brain, which has also become a major defect in the study of brain organoids
.
Today, Nature's blockbuster research finally solved this conundrum by transplanting brain-organoids into rats' developing brains, and finding that they can develop and mature normally, and partially integrate with the brain's neural circuits, truly becoming part of the
brain.
Human induced pluripotent stem cells (hiPSCs) were first selected as the basis for culture, which can culture neurons, astrocytes and microglia
under 2D conditions.
Under special 3D culture conditions, hiPSCs can also develop into different structures such as striatum and cortex, which can be merged to form assembled organoids, which is also a way to
study complex neural circuits.
In the paper, the researchers transplanted cultured human cortical organoids into the cortex of young rats, whose immune systems are defective, so the transplanted organoids are not immune rejected
.
The timing of transplantation is also very critical, and must be completed before the rat's brain neural circuits are fully formed, which can provide a window
for the organoids to develop.
In fact, organoids are desperately integrated into new soils, and even if organoids originated in humans, they will not resist the rat's living environment
.
▲ Human cortical organoids can be transplanted into the rat brain and mature to play their functions (Image source: Reference [1])
According to observations, organoids can develop and mature with the rat's brain, These organoids gradually develop blood vessels to provide nutrients
for their own development.
Gradually, cell types that don't exist in organoids will appear, and specific immune cells like microglia will gradually infiltrate into organoids
.
All this shows that human brain-like organs have formed functional connections and integrated with the rat brain
.
However, organoids do not develop exactly like the human cerebral cortex, and some cell types
are lacking.
But compared with in vitro culture, the transplanted brain-organoid neurons are larger and more closely
connected.
The survival status of transplanted rats is no different from that of ordinary rats, and the proportion of rats that survive for more than 1 year exceeds 70%.
▲ The author transplanted brain organoids to specific parts of rats (Image source: Reference [3])
In addition to normal brain organoids, researchers also tried to use stem cells from patients with Timothy syndrome to grow brain organoids for transplantation
。 The organoid neurons that develop from this are significantly simpler and also have different synaptic connections and electrical activity
.
Of course, the researchers also want to know whether these brain-like organs that have successfully gained a place in rats can function
.
They brought special photosensitive proteins to the cells of the organoids, and neurons could be activated
when stimulated by blue light.
They found that stimulating brain organoids could be used to train rats in reward-related behaviors, such as licking water sources
.
Rats that did not receive transplants did not have a similar response, suggesting that brain organoids were involved in the reward learning process
of rats.
These new results also prove that brain organoids can form suitable and mature tissues in the host, and organoid research has been pushed to a new height
.
In the future, a disease research system that can be closer to reality is coming
towards us.
Reference:[1] Human brain organoids influence rat behavior.
Nature Vol 610 (2022).
[2] A nomenclature consensus for nervous system organoids and assembloids.
Nature (2022).
DOI: https://doi.
org/10.
1038/s41586-022-05219-6[3] Maturation and circuit integration of transplanted human cortical organoids.
Nature (2022).
DOI: https://doi.
org/10.
1038/s41586-022-05277-w
the emergence of induced pluripotent stem cells, which has allowed scientists to make rapid progress in the field of stem cells and developmental biology, and one of the most promising applications is organoids
.
With the differentiation ability of stem cells, researchers can make stem cells form aggregates under 3D conditions, and then orient them towards an organ and tissue
.
These cells eventually self-assemble into miniature, organ-like clumps that mimic livers, kidneys, or brains
.
Brain organoids make neuroscience research more convenient, and scientists can directly manipulate neurons of interest in petri dishes to find the neural mechanisms behind them or potential drug targets
.
Image source: 123RF
However, the brain organoids in the petri dish are not perfect, and the neural tissue is always difficult to fully mature and differentiate correctly, so it will also lack some connections in the real brain, which has also become a major defect in the study of brain organoids
.
Today, Nature's blockbuster research finally solved this conundrum by transplanting brain-organoids into rats' developing brains, and finding that they can develop and mature normally, and partially integrate with the brain's neural circuits, truly becoming part of the
brain.
Human induced pluripotent stem cells (hiPSCs) were first selected as the basis for culture, which can culture neurons, astrocytes and microglia
under 2D conditions.
Under special 3D culture conditions, hiPSCs can also develop into different structures such as striatum and cortex, which can be merged to form assembled organoids, which is also a way to
study complex neural circuits.
In the paper, the researchers transplanted cultured human cortical organoids into the cortex of young rats, whose immune systems are defective, so the transplanted organoids are not immune rejected
.
The timing of transplantation is also very critical, and must be completed before the rat's brain neural circuits are fully formed, which can provide a window
for the organoids to develop.
In fact, organoids are desperately integrated into new soils, and even if organoids originated in humans, they will not resist the rat's living environment
.
▲ Human cortical organoids can be transplanted into the rat brain and mature to play their functions (Image source: Reference [1])
According to observations, organoids can develop and mature with the rat's brain, These organoids gradually develop blood vessels to provide nutrients
for their own development.
Gradually, cell types that don't exist in organoids will appear, and specific immune cells like microglia will gradually infiltrate into organoids
.
All this shows that human brain-like organs have formed functional connections and integrated with the rat brain
.
However, organoids do not develop exactly like the human cerebral cortex, and some cell types
are lacking.
But compared with in vitro culture, the transplanted brain-organoid neurons are larger and more closely
connected.
The survival status of transplanted rats is no different from that of ordinary rats, and the proportion of rats that survive for more than 1 year exceeds 70%.
▲ The author transplanted brain organoids to specific parts of rats (Image source: Reference [3])
In addition to normal brain organoids, researchers also tried to use stem cells from patients with Timothy syndrome to grow brain organoids for transplantation
。 The organoid neurons that develop from this are significantly simpler and also have different synaptic connections and electrical activity
.
Of course, the researchers also want to know whether these brain-like organs that have successfully gained a place in rats can function
.
They brought special photosensitive proteins to the cells of the organoids, and neurons could be activated
when stimulated by blue light.
They found that stimulating brain organoids could be used to train rats in reward-related behaviors, such as licking water sources
.
Rats that did not receive transplants did not have a similar response, suggesting that brain organoids were involved in the reward learning process
of rats.
These new results also prove that brain organoids can form suitable and mature tissues in the host, and organoid research has been pushed to a new height
.
In the future, a disease research system that can be closer to reality is coming
towards us.
Reference:[1] Human brain organoids influence rat behavior.
Nature Vol 610 (2022).
[2] A nomenclature consensus for nervous system organoids and assembloids.
Nature (2022).
DOI: https://doi.
org/10.
1038/s41586-022-05219-6[3] Maturation and circuit integration of transplanted human cortical organoids.
Nature (2022).
DOI: https://doi.
org/10.
1038/s41586-022-05277-w
