December 9, 2022


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Kawalec-Segond: The mouse brain is working –

It is forbidden to bring life to a whole organism of mouse and human. However, the experiments presented in the last pages of pages by neuroscientists and tissue engineers at Stanford University are acceptable. They rely on organ transplantation, that is, transplanting human tissue instead of removed mouse tissue. The team led by Sergio Basca was able to do this with respect to the unknown organ and the most difficult tissue to transplant, namely the brain and its primary component – nervous tissue. The brain was a mouse, and the human nervous tissue was glowing green and able to respond to stimulation with a specific wavelength of light.

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Before we run to yell about “playing with God” and “another Frankenstein,” I encourage you to look at the problem from the side of people who have had such bad luck in their lives that they have had a contact accident with a serious CNS injury, a brain tumor that requires surgery to remove Part of it or even a stroke. Of course, regenerative medicine, including in the central nervous system, is making great strides. that I wrote about before. This does not mean, however, that people who have been affected by the tragedies you mention, and thus lost physical or mental fitness, actually have a solution based on regeneration available to them.

The loss of functional neural tissue is also a serious problem, because brain transplantation – even if it is entirely possible for medical reasons, cannot be performed for ethical reasons. These are the so-called personal bodies. When approaching the matter in a humorous way, one can remember the famous saying of Kornel Makuszyński that it is safer to change hearts than to change heads, because in the latter case you can get sheep as humans.

Seriously, the point is that memory, and much of what we call personality, is hidden in the brain’s structure, as a result of its specific history, and its specific experiences. So a head transplant means, in a sense, that the brain got a new body, and the body doesn’t have a new brain.

Therefore, it is necessary – more often than part of the brain is damaged, to learn how to bridge this defect – to transplant a part of the brain. Of course, the problem is that so-called brain death is the basis for the possibility of recovering other organs that are still viable and functional from someone for transplantation. The dead brain is dead and unfit for cultivation, although good progress has been made in restarting some functions of pig brains within hours of being separated from the rest of the body.

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Yale team of Prof. In 2018, Nenada Šestana was able to connect these pigs’ brains with a special device that nourishes tissues and supplies them with oxygen back to physiological levels. And from living people, no one would take a part of his brain to transplant to other people – that would be very unethical.

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What is left for us? Take care of the Stanford team Culture of human neurons, the so-called small brains. Many things can be studied in a fairly simplified manner and by using various techniques of neurophysiology or neurogenetics. From how the Neanderthal brain functions, through neurodevelopmental disorders and neuropsychiatric diseases (i.e. the spectrum from epilepsy to autism to schizophrenia) or the neurotoxicity of various substances and agents, to working out the potential to grow brain tissue for transplant in humans. Culture is in the form of a three-dimensional, self-organizing mass of functionally functional neural tissue—the little brain.

The necessary neural tissue cells here can be derived from available embryonic stem cell lines or (more ethically, but less effectively) from the normal cells of our bodies that are stimulated to be stem cells (the so-called iPSC). Other genes can also be inserted into such cells, for example so that the tissues formed from them have a mark (glowing green or red) and that – thanks to a technology called optogenetics – certain cells of the organoid behave in a certain way under the influence of not light of a particular wavelength .

Of course, these are not quite small, pea-sized brains, but clumps of living neural tissue grown from precursors. Thus, organelles lack separate functional parts or the connectivity that exists between them in vivo, which limits their maturation and prevents integration with other neural circuits, for example, behavioral control. This is because it works so normally that the specific sensory nerve runs with the information obtained in the future to the median nerve (or many, one by one, associative nerves), and from there again the so-called motor nerve extends towards the responding organ, until the hand that withdraws From the heat that is felt on the skin, there is no such natural stimulation and actions in the exact movements themselves, since they are not connected to any receptors or stimuli.

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However, if they were to be included in the whole, despite the brain damage?

Is the answer to this question left to the neurobiologists at Stanford University? As they describe themselves: “Here we demonstrate that human stem cell-derived cortical organelles transplanted into the somatosensory cortex of newborn rats (so that there is no rejection of such a bait – MK-S) develop mature cell types that integrate with sensory circuits and motivational rodents.” […] In this way, transplanted human cortical neurons mature and engage the host circuits that control behaviour.

So everything “grown” beautifully – it works. Which means, for example, that a trained rat after implantation in response to blue laser stimulation will pass flawlessly to the drinker, because it will feel thirsty.

Simply put, human cortical neurons grown from scratch in the lab affected the behavior of other types of mammals the way they were transplanted. Conversely, they also worked—that is, when the wind moved the mouse’s whiskers, human neurons ignited with activity, and the rest of the mouse’s brain reported the event. To get a full set of results, when scientists implanted mice with organic matter grown from stem cells of patients with serious genetic neurological disorders, they could observe the abnormal development of human neurons against the background of a healthy mouse with unprecedented clarity.

The Stanford lab under Sergei Pace has been working with miniature brains almost since its inception, when in 2013 neurobiologist Madeleine Lancaster of the Austrian Academy of Sciences cultured stem cells in a gel, allowing them to self-organize into a tiny form. , globular masses of working brain tissue. Two years later, the Stanford team obtained small brains that stimulate action potentials, that is, they can be functionally tested. Again, a few years later, the UC Davis Medical Center group published the first small brains to bleed, and opened the door to research into strokes and other cerebrovascular diseases.

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Brain transplantation is not possible and is unethical. But making the patient’s cells his own mini-brain, which, after transplantation at the site of damage, will grow in brain tissue and over time, as a result of rehabilitation work and appropriate stimulation, can try to take on the tasks of the damaged part is a real future.

At the moment, this type of expertise is used for scientific research, determining the neural activities that we are actually dealing with, studying genetically determined neurological diseases, and testing neurotoxic substances for the proper functioning of the brain, which “bare” brain organoids did not provide. However, this is certainly not the end of this story.

The organoids obtained at Stanford University did not form any of the six layers of the normal human cerebral cortex, and their integration into the rat brain was not ideal, because instead of building around other brain structures, human tissue pushed them out. However, the brain is plastic, because the post-implant mice showed no abnormalities on physical and cognitive tests. In order to be able to treat people after strokes or accidents, they have to begin to differentiate into these classes. Today’s results make it possible to believe that it will happen sooner or later. This technology is not even 10 years old.

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