Ancient disease have the surprising ability to regenerate livers

Cellular reprogramming!

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Leprosy, also known as Hansen’s disease (HD), is one of the world’s oldest and most persistent diseases caused by Mycobacterium leprae.

A new study by the University of Edinburgh showed the previously unexplored ability of the bacteria causing Leprosy. Scientists have shown that the bacteria that cause it may also have the surprising ability to grow and regenerate a vital organ. The parasites associated with Leprosy can reprogramme cells to increase the size of a liver in adult animals without causing damage, scarring, or tumors.

Previous studies used an intrusive procedure to promote the regrowth of mouse livers by generating stem cells and progenitor cells. However, the procedure often resulted in scarring and tumor growth.

To overcome these harmful side effects, Edinburgh researchers built on their previous discovery of the partial cellular reprogramming ability of the leprosy-causing bacteria, Mycobacterium leprae.

In collaboration with the US Department of Health and Human Services in Baton Rouge, Louisiana, scientists infected 57 armadillos — a natural host of leprosy bacteria — with the parasite and compared their livers with those of uninfected armadillos and those that were found to be resistant to infection.

They discovered that the infected animals grew enlarged livers that were healthy and uninjured and had the same important organs as the uninfected and resistant armadillos, including blood vessels, bile ducts, and functional units known as lobules.

The team believes the bacteria ‘hijacked’ the inherent regenerative ability of the liver to increase the organ’s size and, therefore, to provide it with more cells within which to increase.

They also discovered several indicators that the main kinds of liver cells — known as hepatocytes — had reached a “rejuvenated” state in the infected armadilllos.

The diseased armadillos’ livers also had gene expression patterns—the instructions for constructing a cell—that were comparable to those of younger animals and embryonic human livers.

Genes connected to aging were inhibited, whereas those linked to metabolism, growth, and cell proliferation were activated.

According to scientists, the reason for this is that the bacteria reprogrammed the liver cells, sending them back to their progenitor stage where they could develop into new hepatocytes and produce new liver tissues.

Scientists look forward to developing interventions for aging and damaged livers in humans.

Professor Anura Rambukkana, a lead author from the University of Edinburgh’s Centre for Regenerative Medicine, said“If we can identify how bacteria grow the liver as a functional organ without causing adverse effects in living animals, we may be able to translate that knowledge to develop safer therapeutic interventions to rejuvenate aging livers and to regenerate damaged tissues.”

Journal Reference:

  1. Samuel Hess, Timothy Kendall, et al. In vivo partial reprogramming by bacteria promotes adult liver organ growth without fibrosis and tumorigenesis. Cell Reports Medicine. DOI: 10.1016/j.xcrm.2022.100820