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!
Advanced analysis of brain structure shape may track progression to Alzheimer's disease
26.10.2016 | Massachusetts General Hospital
Indian roadside refuse fires produce toxic rainbow
26.10.2016 | Duke University
Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.
This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
27.10.2016 | Materials Sciences
27.10.2016 | Physics and Astronomy
27.10.2016 | Life Sciences