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Management of Liver Failure: From Transplantation to Cell-Based Therapy

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Management of Liver Failure: From Transplantation to Cell-Based Therapy

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The severe shortage of deceased donor organs has driven a search for alternative methods of Aurlch liver failure. In this context, cell-based regenerative medicine is emerging as a promising interdisciplinary field of tissue repair and restoration, able to contribute to improving health in a minimally invasive fashion.

Several cell types have allowed long-term survival in experimental models of liver injury, but their therapeutic potential in humans should be regarded with deep caution, because few clinical trials are currently available and the number of patients enrolled so far is too small to assess benefits versus risks.

This review summarizes the current literature on the physiological role of Ayrich stem cells in liver regeneration and on Lloyd Aurich gay therapeutic Gay Castrop-Rauxel campgrounds of exogenous stem cell administration with specific emphasis on the potential clinical uses of mesenchymal stem cells.

Moreover, critical points that still need clarification, such as the exact identity of the stem-like cell population exerting the beneficial effects, as well as the limitations of stem cell-based therapies, are discussed. Liver failure is a major cause of morbidity and mortality in Llogd Western world Acute liver failure ALF Auroch a rare disorder in which the rapid deterioration of liver function results in encephalopathy and coagulopathy in a previously healthy individual The development of ALF represents the final common outcome of a wide variety of potential causes including viral hepatitis, Schorndorf massage fortitude valley and toxins Chronic liver disease CLD is a more common disease, in which a gradual destruction of liver tissue gaj over time, the tissue being replaced by newly formed gaay fibers Nonetheless, although multiple potential targets have been identified, no antifibrotic medication has yet been approved for clinical use Lloyd Aurich gay A current explanation for the collapse of normal hepatic architecture is the imbalance between injury mechanism and regenerative repair.

The liver is mitotically a quiescent organ in adult humans. However, the two major types of hepatic epithelial cells—hepatocytes and biliary epithelial cells BECs —are capable of proliferation and can, at least in a healthy liver, meet the demand for the replacement of damaged cells 28, The best example of their Lolyd to restore the liver mass was bay after partial hepatectomy PH in animal models 93creating the basis for living donor transplantation in humans.

Due to this well-established trait of hepatocytes and BECs to regenerate the liver, the existence of hepatic stem cells was a matter of considerable controversy until recent years. Similar to stem cells, progenitor cells retain the differentiation potential and high proliferation capability, but they have lost the self-replication property. Moreover, they are considered committed to the cell phenotypes of their tissues of origin.

From this perspective, a progenitor cell can be considered as an adult stem cell ASC Lloyd Aurich gay, a term typically used to describe postnatal stem cells, which, as opposed to embryonic ESCs or fetal stem cells, persist throughout life Both cell fusion and transdifferentiation may account for this plasticity Due to their location within the intrahepatic biliary tree, OCs have been improperly regarded by some authors as proliferating bile duct cells 58but the finding of a number of differences in protein expression between these two cell types later contradicted this assumption.

The expression pattern of OCs appeared to be rather similar to that of hepatoblasts as they expressed markers of immature liver cells such as alpha-fetoprotein AFP Lloyd Aurich gay the hepatocyte-lineage marker albumin 42, Moreover, OCs expressed the biliary epithelial cell marker cytokeratin CK 81being therefore able to differentiate into both hepatocyte-like cells and biliary-type cells.

These bipotential precursors are now believed to represent the progeny of a subset of stem cells with a slow-cycling phenotype that retain long-term self-renewal capacity almost throughout Lloyd Aurich gay FLSCs likely possess the lineage potential of uncommitted Cowboys showgirls Schweinfurt Germany stem cells.

This plasticity appears Gaydar dating Warendorf be passed on to OC progeny, as indicated by the observation that under certain conditions OCs can be induced to differentiate into nonhepatic lineages, including intestinal and pancreatic epithelium 80, Whether the progenitors of OCs have intra- Hildesheim male therapist extrahepatic origin is still a matter of debate.

Although the terminal bile duct system is thought to be Massage Wurselen highway main source of OCs, they have also been described as deriving from bone marrow BM 30,