Researching liver disorders is extremely difficult because liver cells (hepatocytes) cannot be grown in the laboratory. However, researchers at the University of Cambridge have now managed to create diseased liver cells from a small sample of human skin. The research shows that stem cells can be used to model a diverse range of inherited disorders and paves the way for new liver disease research and possible cell-based therapy.
Liver disease on the riseIn 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 8-10 percent every year.
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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 10-20 years. In the United States, it accounts for approximately 25,000 deaths a year.
Cell-based therapy?By replicating the liver cells, researchers can not 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 their discovery will lead to tailored treatments for specific individuals and eventually cell-based therapy – when 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, their findings could have implications for conditions affecting other organs.
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 which mimicked a broad range of liver diseases – the first time patient-specific liver diseases have been modeled using stem cells – and to create 'healthy' liver cells from the control group. Importantly, the three diseases the scientists modeled 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 detailing the team’s findings, 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."