A team of Stanford University scientists has successfully transplanted clusters of human neurons into the brains of newborn rats , an unusual feat of biological engineering that may provide more realistic models for neurological conditions such as autism.
It all started 7 years ago
Seven years ago, researchers began an ambitious experiment: They began growing miniature, simplified versions of the human brain from stem cells in a laboratory, then injecting that tissue into the brains of newborn rats. Subsequently, they inoculated the human tissue into the rats’ somatosensory cortices, regions that receive and process sensory information such as touch or pain. All of the rats had dysfunctional immune systems to ensure that the human cells were not rejected.
After about two weeks of training, the rats began to lick a beak in search of water every time the researchers stimulated human neurons. To see if human neurons could influence the rats’ behavior , the researchers used a technique called optogenetics, which involves genetically altering cells so they respond to light (blue light in this case). They also used a puff of air to prick the rats’ whiskers and then watched how the human neurons responded.
At six months, the implanted human minibrain represented about one-third of the hemisphere of the rat brain. The brain was organized into two hemispheres, right and left, each responsible for different functions.
Deep in the rat brain, human and rat cells were connected in the thalamus, the critical area for sleep, consciousness, learning, memory, and information processing from all the senses except smell. .
These models would be as practical for neuroscientific laboratory studies as current animal models are, but much better proxies for human disorders because they would consist of actual human cells in functional neural circuitry. They would even be ideal targets for modern neuroscience tools that are too invasive to use on real human brains.
“This study from Stanford University is very interesting. It is not the first time that human tissues manufactured in the laboratory have been integrated into adult animals, rats or athymic mice (that is, immunodeficient, unable to reject the tissues and cells of another species). This has been done numerous times with different tissues (muscle, skin, blood, nerve tissue, etc.). But yes, to my knowledge, it is the first case of a human brain organoid tissue transplanted into the brain of a newborn rat, with its brain in full development, which shows not only that it is not rejected but that it integrates with its own functions of the rat brain, interconnecting with each other (the authors activate the human cells by rubbing the rat’s whiskers, demonstrating that these cells of the human brain organoid have managed to connect to this somatosensory circuit), and that illustrates a new way of seeing the functional deficits of brain tissue in organoids from patients affected with some neurological disease (the authors demonstrate this with organoids derived from cells from patients with Timothy syndrome, a rare disorder with multiple involvements in various organs and with cardiac alteration as a characteristic symptom )”, explains to Science Media Center Lluís Montoliu , researcher at the CSIC, deputy director of the National Center for Biotechnology ology (CNB).
“It is an amazing experiment and a very significant advance, combining laboratory studies (organoids) with animal studies (organoid transplantation into the brain of athymic rats). This experiment also raises relevant ethical aspects of this research, which should be taken into account and debated in future similar procedures, as brains are somehow generated in these animals that are partially hybrids between neurons of the rat and neurons of the patient used in the process” , concludes the expert.
It only remains to raise the ethical questions of these experiments, such as, for example, the consent of the donors for these purposes (among many other ethical dilemmas).
Referencia: Revah, O., Gore, F., Kelley, K.W. et al. Maturation and circuit integration of transplanted human cortical organoids. Nature 610, 319–326 (2022). https://doi.org/10.1038/s41586-022-05277-w
