Mighty Mice
Human cells were transplanted into the brains of mice to defeat Alzheimer's disease
Anatoly Glossev, Vesti
Biologists transplanted human stem cells into the brains of mice to reproduce the course of Alzheimer's disease on rodents. Experiments have shown that the brain of chimera mice reacts to amyloid plaques causing the disease more like a human than a mouse.
The results of the study were published in the journal Neuron by a group led by Mathew Blurton-Jones from the University of California, Irvine (Hasselmann et al., Development of a Chimeric Model to Study and Manipulate Human Microglia In Vivo).
Methods of treating Alzheimer's disease are extremely difficult to test on animals, since only humans suffer from it. However, in 2017, signs of this disease were first detected in chimpanzees. But this did not make it easier for the doctors. Conducting experiments on creatures capable of assimilating hundreds of words and generally demonstrating the intelligence of a four-year-old child in a number of tests is almost as unthinkable as on humans.
Biologists go to various tricks, trying to recreate the symptoms of the disease in laboratory rodents. But it doesn't turn out very well: many drugs that gave promising results in experiments on such animals failed in clinical trials.
Therefore, this time scientists decided to transplant human cells into the mouse brain. By the way, this is not the first time that biologists have created chimeras, that is, organisms that combine cells of various species.
The researchers did not seek to supply rodents with human neurons. Instead, they reproduced the "auxiliary" tissue of the nervous system – microglia.
"As far as is now known, microglia plays a crucial role in the development and progression of Alzheimer's disease," explains Blurton–Jones in the press release Call it Mighty Mouse: Breakthrough leaps Alzheimer's research hurdle. - The functioning of our cells is affected by which genes [in them] are turned on or off. Recent studies have identified more than 40 different genes associated with Alzheimer's disease, and most of them are included in microglia."
Until now, it has been difficult for biologists to study human microglia affected by Alzheimer's disease. This tissue does not feel well "in vitro". Postmortem microglia samples of deceased patients also make it possible to find out far from all the details that doctors need.
Researchers have implanted human induced pluripotent stem cells into the brains of genetically modified mice. Recall that these are stem cells obtained by "reprogramming" ordinary cells (which in this case were taken from adult volunteers).
A pluripotent stem cell can turn into a cell of any tissue or organ. In this case, scientists have made sure that the transplanted material turns into "bricks" of microglia. A few months after transplantation, tests showed that about 80% of this tissue in the brain of mice consisted of human cells.
The researchers tested how this tissue reacts to amyloid plaques, which are known to provoke Alzheimer's disease. Scientists were interested in which genes are turned on (expressed) in microglia in response to the presence of plaque.
The results were promising. Foreign microglia in rodents expressed genes that are not included in the actual mouse tissue, but, as is known from previous studies, are expressed in patients with Alzheimer's disease.
In addition, microglia migrated to and surrounded the amyloid plaques. The same process occurs in the brain of a sick person.
According to the researchers, mice with human microglia will be useful not only for the study of Alzheimer's disease. They can be indispensable in the study of the consequences and methods of treatment of Parkinson's disease, stroke and traumatic brain injuries.
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