
Hepatic cryoinjury in zebrafish induces a localized necrotic and apoptotic lesion, followed by transient fibrosis and inflammation, which resolves as the liver regenerates within 30 days, providing a reproducible model to study the cellular and molecular mechanisms of fibrosis and regeneration.


coremsg

The liver is a remarkable organ that can regenerate in response to injury. Depending on the extent of injury, the liver can undergo compensatory hyperplasia or fibrosis. Despite decades of research, the molecular mechanisms underlying these processes are poorly understood. Here, we developed a new model to study liver regeneration based on cryoinjury. To visualise liver regeneration at cellular resolution, we adapted the CUBIC tissue-clearing approach. Hepatic cryoinjury induced a localised necrotic and apoptotic lesion characterised by inflammation and infiltration of innate immune cells. Following this initial phase, we observed fibrosis, which resolved as regeneration re-established homeostasis in 30 days. Importantly, this approach enables the comparison of healthy and injured parenchyma with an individual animal, providing unique advantages to previous models. In summary, the hepatic cryoinjury model provides a fast and reproducible method for studying the cellular and molecular pathways underpinning fibrosis and liver regeneration.

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### Competing Interest Statement

The authors have declared no competing interest.

*   AFOG
    :   Fuchsin Orange G
    ALF
    :   Acute liver failure
    APAP
    :   Acetaminophen (N-acetyl-para-aminophenol
    BECs
    :   Biliary epithelial cells
    BrdU
    :   5-Bromo-2-deoxyuridine
    CCl4
    :   Carbon tetrachloride
    DAPI
    :   4′,6-diamidino-2-phenylindole
    DDC
    :   3,5-diethoxycarbonyl-1,4-dihydrocollidine
    DEG
    :   Differentially expressed genes
    DMN
    :   Dimethyl nitrosamine
    Dpci
    :   Days post-cryoinjury
    ECM
    :   Extracellular matrix
    EC
    :   Endothelial cell
    FFPE
    :   Formalin-fixed, paraffin-embedded tissue
    GSEA
    :   Gene Set Enrichment analysis
    HCC
    :   Hepatocellular carcinoma
    HPx
    :   Hepatectomy
    HSCs
    :   Hepatic Stellate cells
    IA
    :   Injured area
    LSEC
    :   Liver Sinusiodal Endothelial Cell
    Mpci
    :   Months post-cryoinjury
    NES
    :   Normalised enrichment score
    NTR
    :   Nitroreductase
    PCNA
    :   Proliferating cell nuclear antigen
    PFA
    :   Paraformaldehyde
    TAA
    :   Thioacetamide
    Ypci
    :   years post-cryoinjury
    Ypci
    :   Years post-cryoinjury

 [1]: pending:yes

Development of a hepatic cryoinjury model to study liver regeneration

cryoinjury-induced-liver-regeneration-a-spatially-localized-model-for-studying-fibrosis-and-tissue-repair


Cryoinjury-Induced Liver Regeneration: A Spatially Localized Model for Studying Fibrosis and Tissue Repair
