Metabolically-Driven Liver Fibrosis

Obesity, hyperglycemia, inflammation driving fibrosis

Standard male and female fibrosis / NASH models

Our model induces a hyperglycemic state by reducing pancreatic beta-cell numbers, thus lowering normal circulating insulin levels (insulin insufficiency) which is exacerbated by a high fat, high fructose diet to induce obesity and systemic inflammation and hepatocyte cell death.  This leads to Hepatic Stellate Cell (HSC) activation to myofibroblasts and subsequent local inflammation culminating in fibrotic remodeling of the liver.

Key Phenotypes Relevant to Human Disease:

  • Hepatic Steatosis, macro- and micro vesicular lipid accumulation  (FLD / NAFLD)

  • Lobular Inflammation, infiltrating macrophages indicative of later stage, more advanced disease

  • Hepatocyte Ballooning Degeneration

Accelerated models

Woodland, in partnership with Taconic Biosciences, has established an accelerated NASH model that will run 10-weeks with up to 8 weeks of dosing, rather than the 20 weeks it takes for our standard NASH model.  We are also working with Taconic to profile their high fat DIO mice for suitability in the NASH protocol. These new assays will be introduced at the 2019 AASLD "The Liver Meeting" and will be highlighted in our new marketing materials. Please inquire for more information.

Enhanced fibrosis with physiologically-relevant insults

Derived from an increasing understanding of "leaky gut" syndrome associated with obesity and the attendant systemic inflammation, Woodland is modeling the increase in NASH parameters induced by these manipulations.  Data will be forthcoming by first quarter 2020 on this modeling.

A second approach is to add a moderate ethanol regimen to the NASH protocol to represent additional insult of alcohol-induced liver injury. We have not established this model but are open to exploring collaborative relationships.

Chemical insult combinations with NASH

For some time now, Woodland has added Thioacetamide (TAA) to our female NASH model along with high fat diet modification to induce an extreme fibrosis, scores of >3 (F3-F4 clinical correlates). Several client compounds have shown significant efficacy in this model over the past year.

TAA and CCl4 can be added to standard NASH or DIO models to exacerbate fibrosis.

Humanized liver mouse steatosis and fibrosis

Under development - see R&D section of the website. Open for partnering opportunities for early access to the model.

Woodland Biosciences

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