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Novel strategies for liver therapy using stem cells
  1. Tamir Rashid1,
  2. Takanori Takebe2,
  3. Hiromitsu Nakauchi3
  1. 1Centre for Stem Cells and Regenerative Medicine and Institute of Liver Studies, King's College London, London, UK
  2. 2Department of Regenerative Medicine, Yokohama City University, Yokohama, Japan
  3. 3Stanford Institute for Stem Cell Biology and Regenerative Medicine, Palo Alto, California, USA
  1. Correspondence to Dr Tamir Rashid, Centre for Stem Cells and Regenerative Medicine and Institute of Liver Studies, King's College London, 28th Floor, Tower Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK; tamir.rashid{at}kcl.ac.uk

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The clinical need

Liver disease is an increasing clinical burden, causing over 10 000 deaths last year in the UK alone (http://www.britishlivertrust.org.uk). Liver insufficiency describes the clinical situation in which cumulative (chronic) or one-off massive (acute) insults exceed the liver's normal physiological capacity to functionally regenerate. Untreated, liver insufficiency invariably leads to death. The current gold standard of care in this setting is whole organ transplantation. Due to the increasing burden of disease within the population, however, the number of patients requiring transplantation far exceeds the number of available donor organs. As a result, many patients with liver insufficiency die prematurely.1

Liver cell therapy-intra vs. extra hepatic

The liver is composed of several cell types (endothelial cells, stellate cells, biliary ductal cells, Kupffer cells and natural killer cells) which together provide a supportive niche for the principle cell type—the hepatocyte.2 Treatment of liver disease by hepatocyte replacement therefore appears a logical alternative to whole organ transplant (figure 1i). Along these lines, intrahepatic hepatocyte transplantation (I-HTx) has repeatedly proven efficacious in small animal models of numerous liver diseases. Results from human applications have unfortunately proven less convincing however with the best, possibly only, positive results observed in paediatric patients suffering from hepatocyte driven inherited metabolic disorders.3 This suggests targeting the surrounding niche may be as important as replacing diseased hepatocytes themselves if one is to treat the majority of liver diseases.4 Such efforts to manipulate the complex nature of the surrounding niche will no doubt be far from trivial. So an alternative, more tangible approach that targets more specific clinical problem could be to use hepatocytes in extra-hepatic anatomical sites to ‘bridge’ patients with liver insufficiency to transplant or self repair (E-HTx).5 Some preliminary clinical experiences suggest a therapeutic effect for alginate-bead encapsulated hepatocytes delivered into the peritoneum of paediatric patients with acute liver failure …

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