Human brain cells can respond to visual sensations when implanted into the brains of rats with brain injuries

In an advance toward the possible future treatment of major brain injuries, human brain cells implanted into injured rat brains were observed responding to visual stimuli.

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Back in October, I posted about scientists from Stanford who put human neurons into rats' brains. In that work, the researchers observed that the human brain organoid was able to grow and form connections inside the rat brain.

There was another study in January where human brain cells were implanted into healthy mice and observed to respond to light.

Today, I read news of a similar study that was published by a team of researchers from the University of Pennsylvania's Perelman School of Medicine and Shenzhen-Hong Kong Institute of Brain Science. The team reported their results in the Open Access journal, Cell Stem Cell on February 2. Here is the paper's Abstract:

Brain organoids created from human pluripotent stem cells represent a promising approach for brain repair. They acquire many structural features of the brain and raise the possibility of patient-matched repair. Whether these entities can integrate with host brain networks in the context of the injured adult mammalian brain is not well established. Here, we provide structural and functional evidence that human brain organoids successfully integrate with the adult rat visual system after transplantation into large injury cavities in the visual cortex. Virus-based trans-synaptic tracing reveals a polysynaptic pathway between organoid neurons and the host retina and reciprocal connectivity between the graft and other regions of the visual system. Visual stimulation of host animals elicits responses in organoid neurons, including orientation selectivity. These results demonstrate the ability of human brain organoids to adopt sophisticated function after insertion into large injury cavities, suggesting a translational strategy to restore function after cortical damage.

In this latest effort, the team also grafted human brain organoids into the brains of rats, and they also observed that the organoids integrated with the nearby rat brain tissue, but the new twist is that the human brain cells were implanted into the brains of rats with major cortical injuries and still observed to function. Within three months of implantation, some of the human brain cells began responding to visual stimulii such as black and white images or lights shined into the rats' eyes.

The corresponding author, Dr. H. Isaac Chen is quoted as saying, "We were not expecting to see this degree of functional integration so early". Chen also noted, that in other studies, it has taken as long as nine or ten months for implanted cells to reach maturity.

In order to implant the human brain cells, the team grew human induced pluripotent stem cells into tiny mini-brains, or organoids. Induced pluripotent stem cells are stem cells that were coerced from adult stem cells back into an undifferentiated state like the one that would be observed in embryonic stem cells. These undifferentiated stem cells were also genetically modified to emit a green fluorescent protein that can be used to observe the cells' activity.

In a process lasting 80 or 90 days, the cells were developed from an undifferentiated state into neurons and then into small organoids. These organoids were then grafted into small cavities that had been hollowed-out in the visual cortexes of the rats' brains, in order to represent a major injury. The procedure was conducted in the brains of ten rats that were subsequently stitched up and allowed to heal after the implantation.

By inserting fluorescent-tagged viruses into the rats eyes and using electrodes, the researchers were able to observe the activity of the inserted cells. In the three-month experiment, about ¹/₄ of the brain cells were observed to be responding to visual stimuli. Chen was further quoted, saying:

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 experiment had to be terminated after three months because they had reached the limit for the immunosuppression technique that kept the rats' bodies from rejecting the human tissue. The team notes that a longer study might have allowed more cells to reach maturity and increased the percentage of cells that became functional. In order to work around this limitation in future studies, the team suggests using rodents that have been genetically engineered with immunosuppression in order to avoid tissue rejection.

Like the study last October, the long term goal of this research is to help humans with brain disorders. Unlike the Stanford work, however, this research is specifically targeted at treatment for brain injuries instead of diseases.

For more information:

• Human Brain Organoids Transplanted Into Rats Just Passed a Major Milestone
• Human brain organoids respond to visual stimuli when transplanted into adult rats
• Structural and functional integration of human forebrain organoids with the injured adult rat visual system
• Human 'Mini-Brains' Implanted in Mice Respond to Light in Scientific First
• Human brain cells transplanted into baby rats’ brains grow and form connections
• Maturation and circuit integration of transplanted human cortical organoids
• A Stanford-led research team connected human neurons to a rat's brain

Thanks for reading!

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Thank you for your time and attention.

As a general rule, I up-vote comments that demonstrate "proof of reading".

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Steve Palmer is an IT professional with three decades of professional experience in data communications and information systems. He holds a bachelor's degree in mathematics, a master's degree in computer science, and a master's degree in information systems and technology management. He has been awarded 3 US patents.

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^{Pixabay license, source}

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