Growth of human tissues in rat brains shows unusual behavior in rats

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A new study published in the journal Nature on Wednesday by a team of researchers from the University of Stanford reveals that the injection of human stem cells in the brains of rats revealed changes in the behavior of rats after a specific period which allowed for the brain cells to mature. 

The study initially began seven years ago with the meticulous experiment of injecting simplified versions of human brain tissues from stem cells into the somatosensory cortexes in the brains of newborn rats. These specific parts of the brain receive sensory information about pain and touch.

With time, the cells matured to reveal patterns of behavior that are usually not observed in normal rats. 

For instance, rats began to lick a spout in search of water whenever their brains were stimulated with the use of blue light lasers. Researchers also used a puff of air to prod the rats’ whiskers, then observed how the human neurons responded.

Sergiu Pașca, one of the study’s authors and a professor of psychiatry and behavioral sciences at Stanford told sources "We found that human neurons respond very quickly after we stimulated the whiskers. In fact, more than 70% of the human neurons are engaged in some form of activity within a second or so of that stimulation, so that tells us that they’re probably connected."

Pașca added that human neurons had become "part of the rat circuitry" and that when stimulated, they were "sparkling" under a microscope. 

Over a period of eight months following the injection, researchers noticed that the human neurons were growing to six times their original size, which occupies almost one-third of a single hemisphere in the rat brains.

Contrary to scientists' expectations, none of the rats showed signs of seizures or epilepsy. Over 70% remained alive after one year following the injection.

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This research is the latest among a series of studies and trials intended to observe the development of human cells in animals.

For instance, in 2006, developmental biologist Ali Brivanlou and a research team from The Rockefeller University grew human embryos in mouse tissue. 

Then, in 2013, a Belgian research team implanted human neurons into newborn mice, which led to the creation of functional brain circuits.

Another research from the Salk Institute for Biological Studies carried out a similar study in 2018 by grafting human brain-like structures in adult mice.

According to Brivanlou, the innovation brought forth by the Stanford study lies in its ability to grow complex, three-dimensional structures that represent the human cortex. 

Brivanlou said that growing such a type of tissue "has not been done very often; in fact, maybe not at the level of precision that this paper is describing."

But scientists rather strived to understand that such a study would provide them with a better understanding of how genetic mutations influence brain circuits and alter behaviors.

It is hoped that the results may assist with certain studies in psychiatric disorders, autism, or neurodegenerative diseases like Parkinson’s or Alzheimer’s, as well as the development of new treatments.

Brivanlou added that this can "open the doors to a tremendous medical and basic understanding of the way the brain works and, at the same time, what happens when things do not work very well."

For instance, they used their research to investigate Timothy syndrome, a rare genetic disorder in humans that can result in life-threatening abnormal heartbeats and may also lead to autism.

The tissues of three people who carry the disease were transplanted into the brains of baby rats.

They observed that these specific cells didn’t grow as large inside the rats and weren't as structurally complex as the other human cells. This proved that the genetic mutations responsible for Timothy syndrome in people slowed the development of the rats’ brains.

But researchers have yet to understand why such mutations change rats’ behavior.

According to Pașca, despite that scientists have a considerable amount of information about the kinds of genes that causes certain psychiatric disorders, they don't have much knowledge about what those genes change inside the brain, or of the nongenetic factors that contribute to neurological disorders.

Hence, the interest in studying Timothy syndrome since it’s caused by the mutation of a single gene responsible for helping the brain process electrical signals. 

Brivanlou did not ignore the ethical questions which accompany such research.

"How much of a human cell can you put in a mouse embryo for that embryo to still be called a mouse? I think this is a very legitimate question that needs to be addressed," Brivanlou said.

However, the benefits might make the experiments worth pursuing.

“If you have a way to save somebody’s life or cure somebody’s disease, or provide at least some sort of a therapy to minimize the pain or extend the life of the person, you should be allowed to exercise that,” Brivanlou said.

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