Health
Leprosy-causing bacteria return liver cells to normal regenerative state
The bacteria that cause leprosy can reprogram cells in adult animals to increase liver size without causing damage, scarring, or tumors, they report. cell report medicine November 15, 2022. Mechanistic insights gained from this study could be used to regenerate aged livers and regrow damaged livers, currently the only treatments for people with end-stage liver disease. It can reduce the need for liver transplantation.
Previous attempts to regrow mouse liver from stem or progenitor cells failed due to scarring and cancer resulting from invasive treatments. To avoid these negative effects, Anura Rambukkana, professor of regenerative medicine, and his team at the University of Edinburgh, UK, Mycobacterium leprae What the team has shown in previous research is that it partially reprograms cells.
“If we can identify how bacteria can grow the liver into a functional organ without harming living animals, we can translate that knowledge to rejuvenate aging livers and repair damaged tissue,” Rambukkana said. We may be able to develop safer therapeutic interventions for regeneration.”
Like humans (and unlike mice), armadillos are the animal’s natural host. M. Leprosy. Therefore, the team decided to use armadillos as an infection model. Rambukkana’s team, working with the U.S. Department of Health and Human Services in his Rouge, Baton, Louisiana, will infect nine-banded armadillos with the bacteria and then transfer the livers of the bacteria-infected armadillos to either uninfected armadillos or those resistant to infection. compared with the liver of an armadillo.The researchers found that the liver M. Leprosy Infected armadillos were larger than control animals. Importantly, despite the overall increase in size, the livers of infected armadillos were healthy and exhibited the same histology as normal livers.
Researchers demonstrated that mature hepatocytes were infected M. Leprosy It undergoes partial reprogramming in vivo to return to an immature state that allows it to divide and reproduce. This bacteria-induced regeneration allows the liver to grow as normal, without the fibrous scar tissue caused by cycles of damage and repair, or by malignancies. and is believed to increase the number of cells in which the parasite can grow and multiply.
to confirm that M. LeprosyAs infected hepatocytes reached a truly rejuvenated state, researchers compared gene expression profiles between infected hepatocytes and hepatocytes from young animal and human fetal livers, revealing similar patterns. did. Infected hepatocytes expressed high levels of genes involved in metabolism, growth and cell proliferation, and low levels of genes associated with aging. M. Leprosy like the liver of young animals and human fetuses. This suggests that the bacterium alters the regulation of hepatocyte gene expression, reverting it to an early progenitor cell state that can differentiate in new liver tissue.
Liver disease currently kills two million people worldwide each year. The team hopes their findings will help develop interventions for aging and damaged livers in humans.
This study was funded by the UK Medical Research Council and the US National Institutes of Health (NIH) and National Institute of Allergy and Infectious Diseases (NIAID).
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