Scientists have grown miniature human brains from skin cells in a laboratory for the first time as part of a study into the development of the most complex of all our organs, and the ultimate source of human creativity and consciousness.
The mini-brains are less than 4mm across but researchers say that they are equivalent in development to the brain of a human foetus at about nine weeks’ gestation, and even have the complex three-dimensional structure of a real embryonic brain.
Previous attempts at growing brain tissue in a laboratory dish have focused on culturing the nerve cells in two dimensions on a flat plate of nutrients, but the latest study used a droplet of nutrient gel as a three-dimensional scaffold on which the growing brain cells organised themselves into the miniature organ.
The scientists have called the primitive brains “cerebral organoids” and have emphasised that the living structures are still far from being described as true human brains with a potential for self-awareness or consciousness – a threshold of development that would be ethically wrong to cross, they said.
“Three or four millimetres do not sound very much, but for someone who is used to working with a microscope it’s quite a lot. The individual brain areas that we find in our organoids are not so very far away from the size of the endogenous organs at this stage of development,” said Juergen Knoblich, of the Institute of Molecular Biotechnology in Vienna.
“It is absolutely not the goal of our work to generate higher-order brain structures. For us, growing them bigger is not the issue. At this size they can hold quite a lot of complexity… this is one of the cases where size doesn’t really matter,” Dr Knoblich said.
The mini-brains were created from human skin cells that were converted into stem cells by a well-established genetic engineering technique. This produced induced pluripotent stem (iPS) cells which were then coaxed by chemical stimulants and nutrients to develop into mature brain cells that self-organised into the rudimentary structures of an embryonic brain, such as the cerebral cortex.
Dr Knoblich said that the organoids have already shed light on a condition called microcephaly, when the brain fails to grow to its correct size in the womb, and also could eventually help research into conditions such as autism and schizophrenia, which both involve unknown malfunctions in early brain development.
“There have been numerous attempts recently to model human brain tissue from human cells. [Scientists] have gone on to generate an eye, a pituitary gland and even a human liver, but so far the most complex of all human organs, which is the brain, has not been susceptible to these kinds of cultures,” Dr Knoblich said.
“[This technique] allows us to study the human-specific features of brain development. We can analyse the function of individual genes in a human setting. We have been able to model one disease, microcephaly, but ultimately we’d like to move to more common disorders such as schizophrenia or autism,” he said.
“So far drug testing has been done on animal models and isolated human cells. These organ-culture models offer the possibility of testing drugs directly without animal experiments to get more informed results,” he added.
The study, published in the journal Nature, showed that it was possible to convert skin cells into a specialised form of embryonic tissue called the neuroectoderm, which produces all the components of the brain and nervous system. Organoids from a patient with microcephaly fail- ed to grow as fast as other organoids, but this could be corrected by replacing a defected gene responsible for the disorder, the study showed.
Andrew Jackson, of the Medical Research Council’s Human Genetic Unit in Edinburgh, who collaborated with Dr Knoblich, said that the brain organoids provides a new way of studying the human brain, the most complex structure known with an estimated 100 billion nerve cells and many times the number of nerve connections.
“Being able to generate tissue with such complexity in cell culture is a significant advance for the study of human disease in the laboratory,” he said.
Oliver Brustle, a stem-cell expert at the University of Bonn, said: “These structures are not just peculiar lab artefacts… the organoids re-create early steps in the formation of the human brain’s cerebral cortex, and so lend themselves to studies of brain development and neurodevelopmental disorders.”
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