Leprosy is one of the oldest and most persistent diseases in the world, but the bacteria that cause it can also have the surprising ability to grow and regenerate a vital organ.
Scientists have found that parasites associated with leprosy can reprogram cells to increase liver size in adult animals without causing damage, scarring or tumors.
The results suggest the possibility of adapting this natural process to renew aging livers and increase lifespan – disease-free life – in humans.
Experts say it could also help regrow damaged livers, reducing the need for transplants, which are currently the only curative option for people with end-stage scarred livers.
Previous studies have promoted the regrowth of mouse livers by generating stem cells and progenitor cells – the step after a stem cell that can become any type of cell for a specific organ – via an invasive technique that often resulted in scarring and tumor growth.
To overcome these harmful side effects, the Edinburgh researchers built on their previous discovery of the partial cell reprogramming ability of the leprosy-causing bacterium, Mycobacterium leprae.
Working with the US Department of Health and Human Services in Baton Rouge, Louisiana, the team infected 57 armadillos – a natural host of the leprosy bacteria – with the parasite and compared their livers with those of armadillos. uninfected and those that have been shown to be resistant to infection.
They found that infected animals developed enlarged – but healthy and unharmed – livers with the same vital components, such as blood vessels, bile ducts and functional units called lobules, as uninfected and resistant armadillos.
The team believe the bacteria ‘hijacked’ the liver’s inherent regenerative ability to increase the organ’s size and, therefore, provide it with more cells in which to grow.
They also found several indicators that the main types of liver cells – called hepatocytes – had reached a “rejuvenated” state in the infected armadillos.
The livers of the infected armadillos also contained gene expression patterns – the model for building a cell – similar to those of younger animals and human fetal livers.
Genes related to cell metabolism, growth and proliferation were activated and those related to aging were downregulated or suppressed.
Scientists believe this is because the bacteria reprogrammed the liver cells, returning them to the earlier stage of progenitor cells, which in turn became new hepatocytes and developed new liver tissue.
The team hopes the discovery has the potential to help develop interventions for aging and damaged livers in humans. Liver disease currently causes two million deaths a year worldwide.
The results were published in the journal Medicine Reports Unit. This work was funded by the UK Medical Research Council and the US National Institutes of Health and National Institute of Allergy and Infectious Diseases.
Professor Anura Rambukkana, lead author from the Center for Regenerative Medicine at the University of Edinburgh, said: “If we can identify how bacteria grow the liver as a functional organ without causing adverse effects in animals alive, we may be able to translate this knowledge to develop safer systems. therapeutic interventions to rejuvenate aging livers and regenerate damaged tissue.
Medicine Reports Unit
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Partial reprogramming in vivo by bacteria promotes growth of adult liver organs without fibrosis or tumorigenesis
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