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Implication for Bone Marrow Derived Stem Cells in Hepatocyte Regeneration after Orthotopic Liver Transplantation

DOI: 10.1155/2013/310612

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Abstract:

The liver has the outstanding ability to regenerate itself and restore parenchymal tissue after injury. The most common cell source in liver growth/regeneration is replication of preexisting hepatocytes although liver progenitor cells have been postulated to participate in liver regeneration in cases of massive injury. Bone marrow derived hematopoietic stem cells (BM-HSC) have the formal capacity to act as a source for hepatic regeneration under special circumstances; however, the impact of this process in liver tissue maintenance and regeneration remains controversial. Whether BM-HSC are involved in liver regeneration or not would be of particular interest as the cells have been suggested to be an alternative donor source for the treatment of liver failure. Data from murine models of liver disease show that BM-HSC can repopulate liver tissue and restore liver function; however, data obtained from human liver transplantation show only little evidence for liver regeneration by this mechanism. The cell source for liver regeneration seems to depend on the nature of regeneration process and the extent of injury; however, the precise mechanisms still need to be resolved. Current data suggest, that in human orthotopic liver transplantation, liver regeneration by BM-HSC is a rather rare event and therefore not of clinical relevance. 1. Introduction Liver diseases are an important cause of morbidity and mortality in both Europe [1] and the USA [2], and the incidence for acute or chronic liver failure is rising due to hepatitis C infections, alcohol abuse, and hepatocellular carcinoma in cirrhosis [3]. Importantly, the liver represents the only vital organ (with exception of the brain) that cannot be replaced by a device because of the complexity of its functions. Orthotopic liver transplantation (OLT) is the treatment of choice for acute or chronic liver failure but is limited by general organ shortage, leading to increased mortality among patients on the waiting list. Although early graft loss as a consequence of primary nonfunction, hepatic artery thrombosis and acute rejection episodes is negligible due to constant improvement of surgical techniques, patient management, and immunosuppressive strategies, bacterial and fungal infections are a major problem being responsible for the majority of patient morbidity and graft loss in the first months after OLT. One-year survival rates for both the patient and graft survival are around 80% [4], with approximately 50% of all deaths happening within the first 6 months. The concept of liver cell transplantation by

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