Researchers have managed to convert skin from individuals with metabolic diseases into liver cells using stem cell technology, according to an article published in the Journal of Clinical Investigation. This research will allow scientists to determine precisely what is happening in a diseased liver cell, then try out potential treatments. The scientists say that eventually properly functioning liver calls might be transplanted into patients with liver diseases.

The researchers, from the University of Cambridge, England, say that by creating diseased liver cells from human skin, they have for the first time demonstrated that stem cells can be used to model a wide range of inherited disorders.

Hepatocytes (liver cells) cannot be grown in the lab, making liver disorder research extremely challenging. However, this new research demonstrates how to create diseased liver-like-cells from individuals with a range of liver disorders.

The research was funded by the Wellcome Trust and the MRC (Medical Research Council, UK).

If you can replicate the cells of an organ, you can:

  • Investigate exactly what is going on in a diseased cell
  • Test how effective new therapies are

The authors hope that this discovery will eventually lead to tailored treatments for specific patients, and eventually cell-based therapy. Cell-based therapy means using the patient’s own cells, curing them, and then transplanting them back.

This process might also be used to model cells from other parts of the body, not just the liver, resulting in eventual treatments for various body organs and diseases/conditions.

Dr Ludovic Vallier of the MRC Centre for Stem Cell Biology and Regenerative Medicine, University of Cambridge, head researcher, said:

Our work represents an important step towards delivering the clinical promises of stem cells. However, more work remains to be done and our group is dedicated to achieving this ultimate goal by increasing the knowledge necessary for the development of new therapies.

Experts believe the UK will have the highest liver disease death rates in Europe by 2012. Liver disease is the 5th largest cause of death in the UK. Over the last three decades mortality from liver disease in young and middle-aged individuals has increased six fold. The number of patients dying from liver disease is growing at 8% to 10% annually.

The researchers inform that liver disease will become the leading cause of death within the next 10 to 20 years, overtaking even stroke and coronary heart disease. In the USA 25,000 patients die from liver disease annually.

In this research scientist took small skin samples (biopsies) form 7 patients – all of them with a range of inherited liver disease. Skin biopsies were also taken from 3 healthy individuals (control group). The skin sample cells were then reprogrammed back into stem cells, which were then used to generate liver cells which mimicked the broad range of liver diseases. This was the first time patient-specific liver diseases have been modeled using stem cells. They also created ‘healthy’ liver cells from the control group.

Significantly, the three diseases the scientists modeled covered a wide range of pathological mechanisms, thus demonstrating the potential application of their research on a wide variety of disorders.

Dr Tamir Rashid, of the Laboratory for Regenerative Medicine, University of Cambridge, lead author of the paper, said:

We know that given the shortage of donor liver organs alternative strategies must urgently be sought. Our study improves the possibility that such alternatives will be found – either using new drugs or a cell-based therapeutic approach.

Professor Mark Thursz (not affiliated to the study), a specialist in liver disease and Professor of Hepatology at Imperial College, said:

“Liver disease is the fifth most common cause of mortality in many developed countries and unlike the other leading causes of death, the rate of liver related mortality is increasing.

The development of patient specific liver cell lines from stem cells is a significant advance in the battle against liver diseases. This technology holds promise in the short term by providing new tools to explore the biology of liver diseases and in the long term as a potential source of liver cells for patients with liver failure.

“Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells”
S. Tamir Rashid, Sebastien Corbineau, Nick Hannan, Stefan J. Marciniak, Elena Miranda, Graeme Alexander, Isabel Huang-Doran, Julian Griffin, Lars Ahrlund-Richter, Jeremy Skepper, Robert Semple, Anne Weber, David A. Lomas and Ludovic Vallier
J Clin Invest. doi:10.1172/JCI43122

Written by Christian Nordqvist