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Human Nonalcoholic Steatohepatitis on a Chip.
May S Freag1,2, Bumseok Namgung1,2, Maria E Reyna Fernandez1,2
1Center for Engineered TherapeuticsDivision of Engineering in MedicineDepartment of MedicineBrigham and Women's HospitalHarvard Medical SchoolBostonMAUSA.
Hepatology Communications
|February 8, 2021
Summary
A novel NASH-on-a-chip platform using human liver cells successfully models nonalcoholic steatohepatitis (NASH) progression and drug efficacy. This innovative model aids in developing new treatments for this growing liver disease.
Area of Science:
- Hepatology
- Biotechnology
- Disease Modeling
Background:
- Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD) lacking specific treatments.
- Current models fail to fully replicate the liver's microenvironment and disease progression.
- Organ-on-a-chip technology offers a promising avenue for disease modeling and drug testing.
Purpose of the Study:
- To develop and validate a microfluidic NASH-on-a-chip platform.
- To recapitulate key cellular and pathological features of NASH progression.
- To assess the efficacy of a potential NASH therapeutic agent.
Main Methods:
- Co-culture of four primary human liver cell types (hepatocytes, Kupffer cells, liver sinusoidal endothelial cells, hepatic stellate cells) in a microfluidic device.
- Induction of NASH-like phenotype through exposure to a lipotoxic environment.
- Evaluation of liver function markers (albumin, urea) and NASH hallmarks (lipid accumulation, ballooning, inflammation, fibrosis).
- Testing the therapeutic effect of elafibranor on the NASH-on-a-chip model.
Main Results:
- The NASH-on-a-chip platform maintained a functional liver microenvironment for over two weeks.
- Lipotoxic conditions induced NASH characteristics, including lipid accumulation, hepatocellular ballooning, and increased inflammatory/profibrotic markers.
- Elafibranor treatment significantly reduced NASH hallmarks, including intracellular lipids, ballooned hepatocytes, and fibrosis markers.
Conclusions:
- A functional NASH-on-a-chip platform was successfully developed, mirroring key NASH histological endpoints.
- This human-relevant *in vitro* model can advance the study of NASH pathogenesis.
- The platform shows potential for non-invasive drug screening and development of novel anti-NASH therapies.
