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Recent evidence indicates that the plasticity of preexisting hepatocytes and bile duct cells is responsible for the appearance of intermediate progenitor cells capable of restoring liver mass after injury without the need of a stem cell compartment. However, mesenchymal stem cells (MSCs) exist in all organs and are associated with blood vessels which represent their perivascular stem cell niche. MSCs are multipotent and can differentiate into several cell types and are known to support regenerative processes by the release of immunomodulatory and trophic factors. In the liver, the space of Disse constitutes a stem cell niche that harbors stellate cells as liver resident MSCs. This perivascular niche is created by extracellular matrix proteins, sinusoidal endothelial cells, liver parenchymal cells and sympathetic nerve endings and establishes a microenvironment that is suitable to maintain stellate cells and to control their fate. The stem cell niche integrity is important for the behavior of stellate cells in the normal, regenerative, aged and diseased liver. The niche character of the space of Disse may further explain why the liver can become an organ of extra-medullar hematopoiesis and why this organ is frequently prone to tumor metastasis. [ABSTRACT FROM AUTHOR]

Ammonia is diffused and transported across all plasma membranes. This entails that hyperammonemia leads to an increase in ammonia in all organs and tissues. It is known that the toxic ramifications of ammonia primarily touch the brain and cause neurological impairment. However, the deleterious effects of ammonia are not specific to the brain, as the direct effect of increased ammonia (change in pH, membrane potential, metabolism) can occur in any type of cell. Therefore, in the setting of chronic liver disease where multi-organ dysfunction is common, the role of ammonia, only as neurotoxin, is challenged. This review provides insights and evidence that increased ammonia can disturb many organ and cell types and hence lead to dysfunction. [ABSTRACT FROM AUTHOR]