In vivo Partial Reprogramming by Bacteria Promotes Adult Liver Organ Growth without Fibrosis and Tumorigenesis

Samuel Hess, Timothy Kendall, Maria Pena, Keitaro Yamane, Daniel Soong, Linda Adams, Richard Truman, Anura Rambukkana

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Ideal therapies for regenerative medicine or healthy aging require healthy organ growth and rejuvenation but no organ level approach is currently available. Using Mycobacterium leprae (ML) with natural partial cellular reprogramming capacity and its animal host nine-banded armadillos, we present an evolutionarily refined model of adult liver growth and regeneration. In infected-armadillos, ML reprogram the entire liver and significantly increase total liver: body weight by increasing healthy liver lobules including hepatocyte proliferation and proportionate expansion of vasculature, and biliary systems. ML infected livers are microarchitecturally and functionally normal without damage, fibrosis or tumorigenesis. Bacterial-induced reprogramming reactivates liver progenitor/developmental/fetal genes, and upregulates growth-, metabolism-, and anti-aging-associated markers with minimal change in senescence and tumorigenic genes, suggesting bacterial hijacking of homeostatic, regeneration pathways to promote de novo organogenesis. This may facilitate the unravelling endogenous pathways that effectively and safely re-engage liver organ growth, with broad therapeutic implications including organ regeneration and rejuvenation
Original languageEnglish
Article number100820
Number of pages45
JournalCell Reports Medicine
Issue number11
Publication statusPublished - 15 Nov 2022


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