Parasites associated with leprosy may have the ability to regenerate livers

Parasites associated with leprosy may have the ability to regenerate livers

Leprosy is one of the world's oldest and most stubborn diseases, but the bacteria that cause it may also have the surprising ability to grow and regenerate a vital organ.

Scientists have discovered that parasites associated with leprosy can reprogram cells to increase the size of a liver in adult animals without causing damage, scarring or tumors.

The results suggest the possibility of adapting this natural process to renew aging livers and extend healthspan - the length of time people live disease-free.

Experts say it could also help re-grow damaged livers, thereby reducing the need for a transplant, which is currently the only curative option for people with end-stage scarred livers.

Previous studies 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 cellular reprogramming ability of the leprosy-causing bacterium Mycobacterium leprae.

Working with the U.S. Department of Health and Human Services in Baton Rouge, Louisiana, the team infected 57 armadillos - a natural host of leprosy bacteria - with the parasite and compared their livers to those of uninfected armadillos and those found to be resistant to the infection.

They found that the infected animals developed enlarged - but healthy and uninjured - livers with the same vital components such as blood vessels, bile ducts and functional units known as lobules as the uninfected and resistant armadillos.

The team believes that the bacteria “hijacked” the liver's inherent regenerative ability to increase the size of the organ and therefore provide it with more cells in which to multiply.

They also discovered several signs that the main types of liver cells - known as hepatocytes - in the infected armadillos had reached a "rejuvenated" state.

The livers of the infected armadillos also contained gene expression patterns - the blueprint for building a cell - similar to younger animals and human fetal livers.

Genes associated with metabolism, growth and cell proliferation were activated and genes associated with aging were downregulated or repressed.

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 grew new liver tissue.

The team hopes the discovery has the potential to help develop interventions for aging and damaged livers in humans. Liver diseases currently cause two million deaths worldwide every year.

The results were published in the journal Cell Reports Medicine. This work was funded by the UK Medical Research Council and the US National Institutes of Health and the National Institute of Allergy and Infectious Diseases.

If we can identify how bacteria grow the liver as a functional organ without causing harmful effects on living animals, we may be able to apply this knowledge to develop safer therapeutic interventions to rejuvenate aging livers and regenerate damaged tissue.”

Professor Anura Rambukkana, lead author, University of Edinburgh Center for Regenerative Medicine

Source:

University of Edinburgh

Reference:

Hess, S., et al. (2022) Partial reprogramming in vivo by bacteria promotes adult liver organ growth without fibrosis and tumorigenesis. Cell reports medicine. doi.org/10.1016/j.xcrm.2022.100820.

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