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In experiments on mice, scientists managed to replace non–functioning cellular "cleaners" - the cause of neurodegenerative diseases
Marina Astvatsaturyan, Echo of Moscow
Chinese scientists from Fudan University in Shanghai have developed three approaches to successfully replace almost all non-functioning microglia. The results of these studies are published in the journal Cell Reports (Xu et al., Efficient Strategies for Microglia Replacement in the Central Nervous System). A popular summary of the work can be read in the press release of Scientists replace malfunctioning 'vacuum cleaner' cells linked to neurological disorders.
Microglia are a special type of immune system cells located in the central nervous system, including the brain, retina and spinal cord. Its main function is to protect the neurons of the central nervous system by capturing pathogens, cancer cells, foreign substances and cellular debris. It is a kind of "vacuum cleaner" used by the immune system to maintain the cleanliness of the central nervous system.
And non-functional microglia is associated with many neurological diseases, such as Alzheimer's and Parkinson's diseases, as well as amyotrophic lateral sclerosis. A promising way to weaken or even prevent these diseases seemed to be gene therapy with the replacement of defective genes that cause the disruption of microglia with normal ones. However, so far all animal experiments have been unsuccessful and stopped long before any clinical trials. Attempts to transplant microglia or bone marrow, the source of future microglia cells, were also unsuccessful. But in a recent study by the same Chinese authors, it was noted that when all existing microglia are removed with special preparations, a small number of remaining cells are capable of multiplying and developing normal microglia. This led scientists to the idea that for the development of a normal microglia, it simply needs to create an empty "niche" where it will become a new microglia.
In three series of experiments, the authors reproduced the niche effect by feeding adult mice for two weeks a drug that suppresses the production of a factor necessary to maintain microglia. When all the microglia disappeared, different donor material was introduced to the animals – the source of cells for the new microglia. In one case it was bone marrow, in another – peripheral blood, in the third – healthy microglia.
The scheme of the experiment. Figure from an article in Cell Reports – VM.
During bone marrow transplantation, healthy microglia in the brain was replaced by 93 percent, in the retina – by 99.5 percent, in the spinal cord – by 93 percent. The effect of peripheral blood was at the level of 80 percent, when transplanting normal microglia, the resulting one was practically indistinguishable from it. The three approaches described have their advantages and disadvantages, in a nutshell – the less available the donor material, the greater the effectiveness of its transplantation.
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