余孟严 Mengyan Yu
Brain Neurons That Do Not Belong Here
Chimeric brains are a technology that involve transplanting human brain cells into animal brains. This provides unique insights into life, development research and disease treatment. However, at the same time, it also brings new challenges and discussions on ethical issues.
The laboratory of Vincenzo De Paola, a researcher at Imperial College London, is conducting a special type of neural chimera research. Despite the breakthrough progress that this research can bring to the scientific community, only a few teams can conduct such research due to technological and ethical factors.
This type of research on chimeras has sparked discussions and concerns among the public and ethicists. Some supporters believe that this system has important implications for human health and disease recovery, while opponents argue that the system touches on ethical gray areas.
Scientists transplanted a human organoid (bright green) into a mouse brain to study how neurons behave in the context of health and disease.
Credit: Abed Mansour
What Is the Motivation For Studying Chimeras?
The brain is the most complex and mysterious part of the human body, controlling every aspect and serving as the most intelligent command center. Scientists have put in a lot of effort to understand and study the workings of the human brain, with specific research focused on the development, connections, and interactions of neurons.
As mentioned in the article earlier, chimeras are a combination of cells from different species, while organoids are structures formed by brain stem cells in 3D culture. They consist of multiple organs and can closely simulate the epigenetic and genetic characteristics of transplanted tissues or organs.
The creation of these two entities combined has played an important role in advancing brain research. It has also provided treatment opportunities and plans for people suffering from diseases.
Over the years, researchers have experimented with chimeras and organoids, continuously combining human elements such as cells and organs with animal bodies. One purpose of this research is to better understand how the human system works, while another is to alleviate the shortage of transplantable organs and seek methods for treating human diseases.
Methods for Studying Human Brain Tissue and Human Brain Development In Vivo
One of the most valuable methods in the field of human brain tissue research in laboratories is the creation of chimeras. To transplant a single neuron into an animal brain, two types of human stem cells, embryonic stem cells, and induced pluripotent stem cells, are used to create neuronal cells for chimeras. Both methods are highly regarded for their potential to develop into any type of tissue in the body and to develop into neurons. If a large brain tissue needs to be transplanted into an animal brain, organoids or assembloids are involved. Researchers convert human skin cells into stem cells and induce them to differentiate into various types of brain cells. These cells are placed in appropriate culture media, where they begin to proliferate and form an organoid similar to the cerebral cortex over time.
Human brain cells and their nuclei were transplanted into mouse brains for two months.
Credit: Raquel Real, Manuel Peter, Rick Livesey and Vincenzo De Paola
It has been found that even after transplanting these organoids into mice that were only 2-3 days old, chimeras continued to form and connect with the mouse brain. These organs continue to grow and eventually occupy one-third of the mouse brain. At the same time, the neurons in these organs form functional connections with the mouse brain circuitry. This means that the mouse brain of newborn mice can receive human neurons and mature them, while integrating these human neurons into local neural circuits that can drive rodent behavior.
Although organoids can be a good way to study brain problems, they still cannot replicate the complexity of the real brain due to various limitations. To overcome these limitations, neuroscientists have begun transplanting human-derived organoids and even assembloids into animal brains for further research and experimentation.
Another way to study brain development is to create human-animal chimeric embryos. One method to perform this technique is to add human stem cells to animal embryos, which is usually done within a few days after fertilization. Another approach is blastocyst complementation, which can produce transplantable organs that may be used for research and treatment of diseases in the future.
Additionally, there are still some unresolved issues, such as whether animal embryos can successfully develop and interact with human organs, such as the pancreas, kidneys or brain regions, until maturity. If human cells are mixed with animal embryos from the beginning, the organism might develop abnormally. However, if a particular growth environment is created for a specific organ or tissue type, human cells can more easily take part in the organism's development.
Organoids, such as this one made from human neurons, have been transplanted into animal brains to study how neurons connect and communicate.
Credit: Ilaria Chiaradia
What Are the Consequences?
There is an ongoing debate among the public and ethicists regarding this type of technology and research system.
Some believe that the use of chimeras could create new models for studying neurological disorders or lead to breakthroughs in research on Down syndrome and Alzheimer's disease.
However, others argue that this raises ethical concerns about the fundamental boundary between humans and animals, as the existence of chimeras may blur this line. The creation of these unfamiliar, semi-human brain organisms implanted into animals may cross our previous cognitive boundaries, causing public anxiety and concerns.
In addition to ethical concerns, there are also concerns about unpredictable behaviour and loss of control of cells after chimeras are formed.
It is important to carefully consider when clusters of human neurons in animal brains should be regarded as having a distinct moral status and emotions.
While research on the human brain will not cease, the discovery of chimeras and related research is an important step for scientists in the field. However, in the face of many difficulties, including complex experimental research as well as ethical and moral risks, caution is needed.
To alleviate concerns, scientists are seeking methods to prevent uncontrollable situations. At the same time, researchers in the field of neural chimeras should share more information about their work and experiments with the public. This can greatly ease public anxiety about unfamiliar research systems.
As research progresses, researchers should also study the proportion of human brain tissue to determine at what stage human features such as emotions and consciousness are not activated in transplanted animal bodies. It is also necessary to consider whether donors are aware and consenting, and if they are informed of the purpose and plans of the research when donating biological materials.
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