Published in Stem Cells and Development
Researchers from the Institute for Stem Cell Research and Regenerative Medicine at the University Clinic of Düsseldorf have established an in vitro model system for investigating nonalcoholic fatty liver disease (NAFLD). The study led by Prof. James Adjaye has now been published in the journal Stem Cells and Development.
Histological section of a liver biopsy of a healthy individual (upper left) and an NAFLD patient (upper right) (1). Lipid droplets are visible as vacuoles. Induced pluripotent stem cells, which express the pluripotency marker OCT4 (middle left, green), are in vitro differentiated into hepatocyte-like cells, characterized by the expression of ALBUMIN (ALB, middle right, red) and alpha-fetoprotein (AFP, middle green right). Unstimulated in vitro derived hepatocyte-like cells do not incorporate lipid droplets (lower left) while they develop massive lipid droplets after stimulation with oleic acid (lower right, green).
Credit: Graffmann N et al.
Nonalcoholic fatty liver disease (NAFLD), also called steatosis, is a dramatically under-estimated liver disease, with increasing incidences throughout the world. It is frequently associated with obesity and type-2 diabetes. Approximately one third of the general population in Western countries are affected, often without even having symptoms.
It is a result of a high caloric diet in combination with a lack of exercise, where the liver starts incorporating fat as lipid droplets. Initially, this is a benign state, which can, however, develop into NASH /steatohepatitis, an inflammatory disease of the liver. Then many patients develop fibrosis, cirrhosis or even liver cancer. However, in many cases patients die of heart failure before they develop severe liver damage.
A major obstacle for NAFLD research was, up to now, that biopsies of patients and healthy individuals were required. The Düsseldorf researchers elegantly solved this problem by reprogramming skin cells into so called induced pluripotent stem cells which they differentiated into hepatocyte like cells. "Although our hepatocyte-like cells are not fully mature, they are already an excellent model system for the analysis of such a complex disease", explains Dr. Nina Graffmann, first author of the study.
The researchers recapitulated important steps of the disease in vitro. For example they demonstrated up-regulation of PLIN2, a protein that covers lipid droplets. Mice without PLIN2 do not become obese, even when overfed with a high fat diet. Also the key role of PPARα, a transcription factor involved in controlling glucose and lipid metabolism, was reproduced in the in vitro system.
"In our system, we can efficiently induce lipid storage in hepatocyte-like cells and manipulate associated proteins or microRNAs by adding various factors into the culture. Thus, our in vitro model offers the opportunity to analyse drugs which might reduce the stored fat in hepatocytes" says Dr. Graffmann.
The team now expands the model using induced pluripotent stem cells derived from NAFLD patients, hoping to discover differences which might explain the course of the disease.
"Using as reference the data and biomarkers obtained from our initial analyses on patient liver biopsies and matching serum samples (1), we hope to better understand the etiology of NAFLD and the development of NASH at the level of the individual, with the ultimate aim of developing targeted therapy options," states Professor James Adjaye, senior author of the current study.
Publication: Graffmann N, Ring S, Kawala MA, Wruck W, Ncube A, Trompeter HI, et al. Modelling NAFLD with human pluripotent stem cell derived immature hepatocyte like cells reveals activation of PLIN2 and confirms regulatory functions of PPARalpha. Stem Cells and Development. 2016.
James Adjaye | EurekAlert!
Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care
Disrupted fat breakdown in the brain makes mice dumb
19.05.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...
For the first time, scientists have succeeded in studying the strength of hydrogen bonds in a single molecule using an atomic force microscope. Researchers from the University of Basel’s Swiss Nanoscience Institute network have reported the results in the journal Science Advances.
Hydrogen is the most common element in the universe and is an integral part of almost all organic compounds. Molecules and sections of macromolecules are...
22.05.2017 | Event News
17.05.2017 | Event News
16.05.2017 | Event News
22.05.2017 | Materials Sciences
22.05.2017 | Life Sciences
22.05.2017 | Physics and Astronomy