2023-05-19 01:10:33
Science is capable of surprising things: genes are cut and pasted to get, for example, mosquitoes that do not spread malaria; ‘chimera embryos’, hybrids between humans and monkeys, are created to study the first moments of life; or all kinds of organs are ‘cultivated’ to test medicines or understand diseases.
Of the latter, among the entire range of those named organoids, the most striking are the brains. Actually, mini-brains, a controversial term that, while making surprising headlines, creates a stir among scientists, who are still debating what to call them. Simply explained: these are groups of cells that grow in a petri dish, clump together, and end up functioning in a similar way to processes that occur inside our heads.
At the moment, they are not complete brains; but they serve as simplified and miniature models (they measure just a few millimeters, looking similar to a grain of rice) with which to experiment, and with which achievements ranging from mini-brains to which they have grown ‘eyes’ have already been achieved. ‘ to implants in the minds of mice, which opens the door to a whole scientific revolution.
It all starts with something as simple as a piece of human skin, the same fabric that we leave every night between the sheets of our bed. Scientists are able to ‘reprogram’ or ‘rewind’ these cells and bring them to a previous state, similar to stem cells, when they have the ability to become any type of cell in our body.
Later, they are ‘forced’ to evolve into other more specialized units, creating neurons that interact with each other. From here, a world of possibilities opens up in the laboratory based on a fairly simple raw material to carry out all kinds of tests that could not be done on a living human brain.
No son Frankensteins
“The goal is not to create Frankensteins,” warns ABC Víctor Borrell Franco, a researcher at the Institute of Neurosciences, a mixed center owned by the Higher Council for Scientific Research and the Miguel Hernández University (CSIC-UMH). He speaks with knowledge of the facts: thanks to the mini-brains, his team has discovered a gene that caused our cerebral cortex, the largest and most complex part of our brain, to grow three or four million years ago, turning us into humans . The finding was published in the journal ‘Science Advances‘.
His field, embryonic development –the study of how our very first cells function, when we barely measure as a pea–, is one of the most prolific in terms of the use of mini-brains. Among the explosion of research, the world’s media echoed some mini-brains with ‘eyes’, some ‘showy’ organoids created to study the origin of sight.
Published in the magazineCell Stem Cell‘, the experiment consisted of growing optic cup organoids – the structures from which almost the entire eyeball develops – albeit with a small addition: along with mini-brains. Like human embryos, at 50 days of development, these mini-brains showed clearly visible ‘eyes’.
In the image you can see the ‘mini-brains’ to which ‘eyes’ have been born. Actually, they are optic cups, the precursor organs of vision in embryos
Not only that: these optic cups contained different types of retinal cells, which were organized into neural networks that responded to light, and even contained lenses and corneal tissue. Furthermore, the structures showed that the sort of ‘retina’ of these organoids was connected to the mini-brain.
Creating Human Skin Organoids
30th
Eyes are created inside the neurosphere
Previous step
human skin cells are collected
day 0
They ‘rewind’ until they become an induced pluripotent cell (which behaves like stem cells)
10th day
The neurosphere, a group of nerve stem cells, forms
day 60
The eyes are visible and sensitive to light.
Fuente: Gabriel et al., Cell Stem Cell , 2021 / ABC
Creating organoids
of human skin
Previous step
human skin cells are collected
day 0
They ‘rewind’ until they become an induced pluripotent cell (which behaves like stem cells)
10th day
The neurosphere, a group of nerve stem cells, forms
30th
Eyes are created inside the neurosphere
day 60
The eyes are visible and sensitive to light.
Fuente: Gabriel et al., Cell Stem Cell , 2021 / ABC
Its usefulness does not end in finding out how organs are formed in our mother’s womb. There are also experiments that could have direct applications in medicine in the not too distant future. Borrell Franco points, for example, to a study published in ‘Nature‘ from Cambridge scientists who grew these mini-brains together with a spinal cord from a mouse.
Within a few days of being placed in a Petri dish surrounded by muscle tissue, the organoid generated long neural connections to the bone marrow to connect with it, forming something similar to a central nervous system. It was even able to contract the muscles around it, like the motor neurons in our brains do. «This could be the door to which, in the future, patients who, for example, suffer a stroke, where part of their brain dies, can choose to regenerate those areas with organoids created from their own skin cells. It is a field, without a doubt, promising ».
One of the most groundbreaking latest studies, published in the same magazine At the end of last year, it went a step further: the group led by Sergiu Pasça, a researcher at Stanford University and one of the most relevant figures in work with organoids, managed to insert these mini-brains from human cells into rat brains. and that, in addition, this graft would react when the animals received a reward.
Transplanted human organoid labeled with a fluorescent protein in a rat brain section
“It was a milestone because these organoids do not create connective tissues, such as veins and arteries, so transplanting them into living organisms is very complicated,” Guillermina López-Bendito, also a researcher at the CSIC-UMH Institute of Neurosciences and laboratory collaborator, explains to ABC. of Passa. The key was to include these organoids in the exact place and moment: in the somatosensory cortex – the area responsible for receiving and processing sensory information from the whole body, such as touch – of young rats, whose neural circuits are not yet fully formed.
“It is a revolutionary field and one of the most important methodological advances of this century,” says López-Bendito, who will shortly begin cultivating these mini-brains to study brain diseases, his specialty. “It will allow us to observe genes related to certain pathologies, such as epilepsy, and see what is wrong. Or observe phenomena ‘in vivo’ that are now impossible to observe in living brain samples or in embryos.”
Still ‘in diapers’
She also points out that in the future, these organoids (although she prefers Pasça’s terminology, who considers them asembloid, since they do not form the entire organ) will serve to replace animal tests. “We will be able to use them to test different drugs and make a prediction of how they will work in the human brain. It is true that there will always be a difference with real humans, but it will be a very powerful tool for doing proofs of concept.”
However, both Borrell and López-Bendito agree that these asembloids, organoids or mini-brains are certainly still in their infancy. “We still have to reproduce some types of neuronal cells such as those produced in the thalamus or the striatum of the spinal cord,” says the researcher. “In addition, it will be necessary to address the debate on certain ethical aspects.” For example, issues still lie ahead, such as obtaining human biomaterials or the consent of donors. In addition, many have raised the limits of consciousness, a barrier without even delimiting.
Brain organoids in a petri dish
To address these issues, the US National Academies of Sciences, Engineering, and Medicine released a report in 2021 noting that “it is extremely unlikely that brain organoids possess capabilities that, given current understanding, would be recognized as consciousness, emotion or the experience of pain. That is to say, they doubt that these mini-brains can feel. In addition, they indicated that, as currently created, “does not differ at present from other tissues or in vitro human neural cultures”, which are also used for research. Despite everything, they warned that, as technology advances, “this concept may need to be revised.”
For his part, Borrell indicates: “The brain is an interconnected organ much more complex than what we are creating in the laboratory and about which we still have more questions than answers.” What is inside our heads, for now at least, has no ‘in vitro’ replica.
#Brains #grow #laboratories