Modeling Nonalcoholic Fatty Liver Disease (NAFLD) with Advanced 3D Cell Culture Models

As experts in 3-D cell culture modeling and assessment, Visikol recognizes the challenge of investigating the complex etiology of inflammatory liver diseases.  The urgency of Nonalcoholic Fatty Liver Disease (NAFLD) is underlined by its increasing global prevalence against the backdrop of a lack of therapeutics. Visikol assists its Clients with researching the pathophysiology of the disease as well as potential NAFLD therapeutic treatments through the use of its unique liver 3D cell culture models.

Prevalent throughout the world, NAFLD is observed in all ethnicities, genders and reaches most age ranges. In the last 20 years, there has been a rise in global incidence, up 20-fold, affecting one out of every four people. Increasing to epidemic proportions within the USA, NAFLD currently affects up to 40% of the population or 100 million Americans, and is predicted to affect up to 60% by 2030.

As NAFLD affects so many people, it is perplexing that many foundational questions remain unanswered including:  what are the exact mechanisms of the pathogenic progression; what research models are there that encompass its numerous risk factors; what are the most proficient clinical diagnostic tools; how to detect early disease; how to identify patient populations at the highest risk or those with the poorest prognosis; and importantly, what therapeutics are being developed as currently no effective treatment exists.

The liver is a vital organ as it functions to balance our intake and storage of nutrients versus the body’s energy requirements.  The liver is responsible for the break down and elimination of any unwanted substance within the body.  The change in NAFLD incidence has been attributed to the imbalance of a high sugar plus high fat diet coupled with a more sedentary lifestyle.  Furthermore, disease progression is not well understood due to varying levels of complicating risk factors such as: obesity, type 2 diabetes, hypertriglyceridemia, and metabolic syndrome and possibly genetic factors.

Nonalcoholic fatty liver disease, NAFLD, is a single reference encompassing many histological findings related to hepatic fat accumulation associated with the specific risk factors listed previously, but not alcohol intake, infections, or medications.  NAFLD is related to numerous fatty liver disease subsets: nonalcoholic fatty liver, NAFL; nonalcoholic steatohepatitis, NASH; NASH cirrhosis and hepatocellular carcinoma.  Hepatic steatosis or fat accumulation in the hepatocyte vacuoles is the defining characteristic of NAFL, which may lead to the more pathological condition of NASH, steatosis with injurious hepatocyte ballooning.  Advanced progression of NAFLD is viewed as the development of hepatocellular carcinoma or NASH cirrhosis wherein fibrosis has occurred: damaged liver tissue is replaced with nonfunctional scar tissue. Without therapies specific for NAFLD and with extensive liver fibrosis, the level of liver impairment becomes unsustainable and liver transplant is required.

Although pharmaceutical investments into NAFLD development, drug discovery and clinical diagnostics are on the rise due to the high incidence; one key impediment is the development of a research model reflecting the complexity of the liver as well as the intricacies of its functions.  Cell culture models must demonstrate physiologically relevant biological mechanism including general cell function, cell numbers, differentiation and morphology, viability and proliferation, response to stimuli, and protein synthesis.  Recently, such modeling has evolved to more advanced 3-D systems.  Visikol has successfully pursued the development of liver organoid models uniquely suited to assess NAFLD pathophysiology as well as assessment and identification of drug candidates.

Visikol is committed to meeting our Clients’ ultimate goal of accelerating drug discovery for NAFLD through the use of advanced in vitro models as well as imaging and image analysis tools to effectively study these models. For example, Visikol has several 3D cell culture models such as its HepaRG™ NP 3D liver model which contains multiple liver cell subtypes to effectively model NASH/NAFLD. Along with its high content screening, Visikol’s adaptable liver model and analytical capacity extends the level of supportive research throughout the continuum of NAFLD including lipid deposition, inflammation, extracellular collagen deposition and fibrosis, and adjacent deleterious processes.


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