Liver cells created from patients' skin cells
26 August 2010
Researchers from the University of Cambridge hope the findings, published today in 'The Journal of Clinical Investigation', will eventually lead to new treatments for those suffering from liver diseases.
Liver cells (hepatocytes) cannot be grown in the laboratory, which makes researching liver disorders extremely difficult. However, this new research, funded by the Wellcome Trust and the Medical Research Council (MRC), demonstrates how to create diseased liver-like cells from patients suffering from a variety of liver disorders.
By replicating the organ's cells, researchers cannot only investigate exactly what is happening in a diseased cell, they can also test the effectiveness of new therapies to treat these conditions. It is hoped that this discovery will lead to tailored treatments for specific individuals and eventually cell-based therapy, where cells from patients with genetic diseases are 'cured' and transplanted back. Additionally, as the process could be used to model cells from other parts of the body, the findings could have implications for conditions affecting other organs.
Dr Ludovic Vallier of the MRC Centre for Stem Cell Biology and Regenerative Medicine, University of Cambridge, principal investigator of the research, 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."
In the UK, liver disease is the fifth largest cause of death after cardiovascular, cancer, stroke, and respiratory diseases. Over the past 30 years mortality from liver disease in young and middle-aged people has increased over six times, with the number of individuals dying from the disease increasing at a rate of eight to ten per cent every year.
By 2012, the UK is expected to have the highest liver disease death rates in Europe and, without action to tackle the disease, it could overtake stroke and coronary heart disease as the leading cause of death within the next ten to 20 years.
For their research, the scientists took skin biopsies from seven patients who suffered from a variety of inherited liver diseases and three healthy individuals (the control group). They then reprogrammed cells from the skin samples back into stem cells. These stem cells were then used to generate liver cells that mimicked a broad range of liver diseases - the first time patient-specific liver diseases have been modelled using stem cells - and to create 'healthy' liver cells from the control group. Importantly, the three diseases the scientists modelled covered a diverse range of pathological mechanisms, thereby 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, a specialist in liver disease and Professor of Hepatology at Imperial College London, commented on the importance of the research: "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."
Image: Venous arrangement of the liver; Spike Walker, Wellcome Images
Reference
Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells. Journal of Clinical Investigation; 25 Aug 2010.
