Survivors of sepsis often have severe neurological and muscular sequelae. The use of cell therapy is proving to be an encouraging therapeutic avenue.
Globally, a person dies every 3 to 4 seconds from sepsis. In industrialized countries like France, sepsis claims as many victims as a myocardial infarction. And within fifty years, the number of cases could double due to the aging of the population.
Sepsis is a generalized inflammatory reaction, in response to severe infection. It can start locally, like a urinary tract infection or pneumonia, and then spread throughout the body. “If, thanks to advances in medicine and in particular resuscitation, mortality linked to sepsis is decreasing […] patients who survive have serious sequelae, particularly neurological and muscular, which severely handicap them and permanently prevent them from regaining a normal active life, ”explains the Institut Pasteur, which published this Tuesday in Nature Communication the first results of an innovative cell therapy.
Long-lasting cellular damage
Researchers at the Institut Pasteur first set about understanding the muscle damage observed in patients. They then studied mice suffering from sepsis, and observed damage in the stem cells that cause muscle cells, called satellite cells. Specifically, they observed that within these cells, the mass of mitochondria – structures in charge of providing energy to the cell – drastically fall.
“Scientists have thus shown that after sepsis, the few mitochondria remaining in satellite cells barely allowed them to maintain minimal survival function, but were not sufficient to ensure their division and differentiation into muscle cells in the event of need (muscle growth, repair and maintenance), ”explains the Institut Pasteur. Thus, this impairment prevents the body from restoring lost muscle functions.
This discovery prompted researchers to consider stem cell transplantation as a therapeutic avenue. To develop this cell therapy, scientists selected mesenchymal stem cells (MSCs) as they grow easily in the laboratory and are known for their immunomodulatory properties.
Human trials
Here again, the mouse model was chosen to test the effectiveness of this treatment. Performed directly after septic shock intramuscularly, grafting can reduce the inflammatory response and associated symptoms (fever, weakness …). Researchers also show that mesenchymal stem cells support satellite cells and help them protect the function of mitochondria. Once their mission is complete, it seems that the CSMs are eliminated by the organization.
The researchers now hope to be able to test the effectiveness of their cell therapy in humans. The first phase of this work would make it possible to know whether the same cellular damage is observed in patients; it should start soon.
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