November 15, 2022

expert reaction to study looking at leprosy bacteria and regenerating liver cells in armadillos

A study published in Cell Reports Medicine looks at leprosy bacteria and liver organ growth in armadillos.

Prof Malcolm Alison, Honorary Professor, University of Edinburgh, said:

“Ageing is one of the greatest obstacles to successful liver regeneration in people with chronic liver disease – the liver becomes senescent and fails to register the need to replenish lost tissue.  This study appears to show that it is possible to reverse/reprogram this process, while reactivating the machinery for rejuvenating old cells that would otherwise be refractory to the need for new tissue.  This is essentially a proof of principle study using an infection model in Armadillos, a long-lived species that tolerates infection without any seemingly deleterious effects on the liver.  Importantly the livers got larger without accompanying pathology (cancer or cirrhosis), though we should remember that most mammalian livers stop enlarging once they have reached their normal size, unlike the situation described here.  Nonetheless, knowledge of processes that reactivate the likes of stem cells in adult tissues could represent a milestone in regenerative medicine.”

Dr Darius Widera, Associate Professor in Stem Cell Biology and Regenerative Medicine, University of Reading, said:

“This is an exciting study demonstrating that under certain circumstances, fully specialized armadillo liver cells can be reverted to a juvenile state and regenerate adult armadillo liver tissue.  The authors have used an experimental approach they originally developed to rejuvenate cells of the nervous system in a dish.  Briefly, they exploited infection with leprosy-causing bacteria to achieve a cellular reprogramming of the liver cells to a premature state.  This caused the livers to grow without tumour formation or changes in the organ architecture.

“Overall, the results could pave the way for new therapeutic approaches to the treatment of liver diseases such as cirrhosis.

“However, as the research has been done using armadillos as model animals, it is unclear if and how these promising results can translate to the biology of the human liver.  Moreover, as the bacteria used in this study are disease-causing, substantial refinement of the methods would be required prior to clinical translation.”

Dr Zania Stamataki, Associate Professor, Centre for Liver and Gastrointestinal Research, University of Birmingham, said:

“This is exciting research and unusual in that it shows liver growth in the absence of liver injury.  This research represents an innovative example where we can use microbes as tools to understand biology.

“Most advances in liver regeneration to date have been made using mouse or rat models, which have a short life span and are not suitable to study liver growth in the absence of injury.  The nine-banded armadillo model shows clear evidence of liver enlargement following ML (Mycobacterium leprae) infection, in the absence of liver scarring or any evidence of tumour formation.

“It is important to understand how ML boosts liver growth in these healthy conditions, and if this is also possible in conditions of acute and chronic liver injury.

“This is a promising model and exciting research with the potential to uncover new molecular pathways for liver regeneration that may be applicable in human livers.”

‘In vivo partial reprogramming by bacteria promotes adult liver organ growth without fibrosis and tumorigenesis’ by Samuel Hess et al. was published in Cell Reports Medicine at 16:00 UK time on Tuesday 15 November 2022.

DOI: 10.1016/j.xcrm.2022.100820

Declared interests

Prof Malcolm Alison: “No conflicts of interest.”

Dr Darius Widera: “I have no conflicts of interest to declare.”

Dr Zania Stamataki: “My lab has a long-standing interest in liver regeneration, but we are not working on any pathways or models described in this work, so we have no conflict of interest.”