Human brain tissue was transplanted into rats at Stanford University School of Medicine, where it integrated well and may help advance our knowledge of brain illnesses and the development of novel medications to treat them.
The research took seven years to complete and entailed lengthy ethical arguments over animal welfare and other concerns; it was published in the journal Nature on Wednesday. Immediate implications of the work include exploring causes and treatments for autism, epilepsy, schizophrenia, and intellectual impairments.
Human brain tissue used for implantation was grown in the lab using a process that converts ordinary skin cells into a substance very similar to embryonic stem cells, which are the precursors of all other cell types and are essential to embryonic development. Scientists can coax these cells along the developmental route in the lab, allowing them to mature into any of the human body’s 200 or so cell types.
Researchers formed clusters of these cells to represent various brain regions. Some of the most complex mental operations, including as language, memory, cognition, learning, decision-making, emotion, intellect, and personality, are supposed to take place in the brain’s outermost layer, the cerebral cortex, which the aggregates, known as organoids, resembled.
The human brain tissue was injected into the brains of two- to three-day-old rat pups by the scientists using syringes. Cells from the rat brain traveled to the human tissue and established connections, so integrating the human cells into the rat’s neural circuitry.
The human brain tissue transplanted into the rat-sized around a fifth of an inch, but after six months, it had grown to fill nearly one-third of the rat’s cerebral hemisphere. The right and left sides of the brain perform distinct but complementary roles.
The thalamus, located deep inside the rat’s brain, is essential for sleep, awareness, learning, memory, and processing information from all of the senses except smell. Human and rat cells linked there.
Pasca claimed that before doing any studies on animals, researchers had thorough conversations with ethicists regarding the animals’ well-being. He said there was no indication that the research rats experienced fear, discomfort, or convulsions.
While Japanese stem cell pioneer Yoshiki Sasai is credited with creating the first neural organoid in 2008, Lancaster noted that their influence was limited since they lacked a functional vascular system. The organoid cells were agitated and eventually died due to this lack.
The Timothy syndrome is a hereditary disorder that affects one in a hundred individuals; the Stanford researchers used skin cells from a patient with the disorder to conduct an experiment. Researchers used the capacity to differentiate skin cells into other kinds of cells to make organoids of the patient’s brain, which they then transplanted into the rat’s brain.
They used organoids from a healthy human donor to transplant into the opposite hemisphere of the same rat’s brain to draw comparisons. At five to six months, the cells affected by Timothy syndrome were found to be much smaller and engaged in extremely distinct electrical activity compared to those of healthy brains.
He claimed the Stanford team has shown the feasibility of implanting human brain organoids into a rat’s brain and influencing the animal’s behavior.
To do this, scientists performed a complicated experiment in which they grouped human brain cells together and modified them such that individual neurons could be activated by a distinct wavelength of blue laser light. They were then injected into the brains of rats, and three months later, researchers inserted ultrathin fiber-optic cables into the rodents’ brains to shine blue light on the tissue.
The rodents were housed in clear plastic containers equipped with a watering hole. After priming the rats’ brains with a jolt of blue light, the researchers fed them water only when the rodents showed a positive response. To prove that the transplanted human cells were now a part of the intricate reward-seeking machinery in the rats’ brains, they learned to link the blue light with getting water.