Study finds bacteria of the chronic infectious disease reprogrammed certain cells into ‘stem-like cells’
Leprosy has long been associated with a life of ostracism. However, the bacteria causing this debilitating disease may offer some hope on the regenerative medicine horizon.
A group of researchers have found that armadillo livers grew substantially when infected with Mycobacterium leprae. The surprise doesn’t end there — the pathogen was able to maintain liver function and keep its exquisite architecture intact, giving rise to something that looked like stem cells.
Scientists from the University of Edinburgh and the US Department of Health and Human Services published the study in the journal Cell November 15, 2022. Its foundation is a 2013 paper led by Professor Anura Rambukkana, the chair of regeneration biology at the University of Edinburgh.
This paper, also published in Cell, documented the in-vitro discovery of Mycobacterium leprae’s ability to reprogramme adult Schwann cells, the bacteria’s preferred host niche in the peripheral nervous system, “to a stage of progenitor/stem-like cells”.
The unexpected findings were met with much furore, but Rambukkana was trying to answer only one question: Can we ever be able to show this bacterial-induced reprogramming in animals or humans naturally?
After the study was published, many predicted several new avenues and implications in infection and regenerative medicine fields, Rambukkana said in a conversation with Down to Earth (DTE).
“This question really kept me awake at night for almost two years after we published our paper. It is my obligation as a scientist to prove that this is happening during natural infection,” he added.
Armadillos came into the picture because they are among the few animals that leprosy bacteria infect. The findings were astonishing.
The bacteria was performing something akin to ‘biological alchemy’ — a bacterial pathogen was changing the biology of infected cells to become more ‘valuable’ such that it can promote the growth of a vital organ like the liver in living animals.
No currently available cell therapy can rival this mysterious mechanism, which Rambukkana describes as a natural process stemming from evolutionary training. The leprosy bacteria need functional cells to function within it because of its dependency on the host to survive and replicate.
The bacteria have evolved and perfected the system to grow the tissues for them to live, Rambukkana said, adding: “I am not sure how laboratory-trained cells could do such a complex assembly process, keeping everything perfect, maintaining the architecture and the function and putting them in the right place and order.”
Several researchers remain sceptical about how the leprosy bacteria will impact a human liver, while others point out that a longer-term study is needed to gauge any adverse effects. Since the bacteria’s functions do not involve tumour formation or any adverse effects like fibrosis, it appears safe for now.
Now that this ability has been identified, the next step is to understand its mechanism. “We need to find the mechanisms of how bacteria promote liver growth and then translate that knowledge to develop safer regenerative therapeutics,” Rambukkana told DTE.
It is also possible other bacteria may have a similar function. The authors of this study hope their work will encourage other researchers to explore the ‘good side’ of bacterial pathogens for new kinds of therapeutic development.
But there is still a long way to go in terms of these findings being revolutionary for regenerative medicine.
“If we could harness the bacterial ingenuity, the way they hijack the high regenerative capacity of the adult liver, not the use of bacteria as a whole and apply that knowledge to develop strategies to promote organ level growth, keeping architecture of the organ intact for proper function, then certainly such strategies would revolutionise the field of regenerative medicine,” Rambukkana said.
If successful, this discovery may be lifesaving for the two million annual deaths due to liver disease for which there is no licensed therapy.
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