Generation of Hepatic Stellate Cells from Human Pluripotent Stem for in vitro liver fibrosis studies
Scope of the method
- Human health
- Basic Research
- Translational - Applied Research
- In vitro - Ex vivo
- Human derived cells / tissues / organs
- Pluripotent stem cells
- Hepatic stellate cells
- Liver spheroids
- In vitro liver model
- Non-parenchymal cells
- Liver fibrosis
- Disease modelling
- Toxicity assessment
We established a protocol to efficiently generate hepatic stellate cells (HSCs) from human pluripotent stem cells (PSCs). Our procedure generated complex in vitro spheroid cultures that better mimic the complexity of the liver as well as liver function. In co-culture, iPSC-HSCs promote maintenance of hepatocyte metabolic functionality while being able to respond to hepatocyte-mediated toxicity, activating and promoting intra-spheroid fibrogenesis, one of the main drug-associated adverse liver outcomes. iPSC-HSCs display functional and phenotypic features of human primary cultured HSCs, indicating that they may be a highly suitable cell source of human HSCs for culture-based studies.
- - Incubator,
- - Cell culture hood,
- - Flow cytometer,
- - Laser Scanning Confocal microscope.
- Published in peer reviewed journal
Pros, cons & Future potential
- - Protocol is highly robust,
- - Yields 70%–80% iPSC-HSCs,
- - Highly reproducible.
In 2D the responsive of iPSC-HSCs to external signals is rather limited. Thus far, the method has been used successfully in 3 different institutes using 3 different hESC/hIPSC cell lines, but more should be tested.
Higher throughput and better quality control for the different stages of hiPSC to HSC differentiations.
Can be used for several applications, such as developmental studies, fibrosis modeling, drug screening, liver spheroid generation, and, eventually, regenerative medicine.
References, associated documents and other information
Coll, Mar et al. Generation of Hepatic Stellate Cells from Human Pluripotent Stem Cells Enables In Vitro Modeling of Liver Fibrosis. Cell Stem Cell, Volume 23, Issue 1, 101 - 113.e7
Contact personLeo A. van Grunsven
OrganisationsVrije Universiteit Brussel
Liver Cell Biology research group