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- BM, bone marrow
- BMSC, bone marrow stem cell
- BMT, bone marrow transplantation
- CCl4, carbon tetrachloride
- EMT, epithelial mesenchymal transition
- EPC, endothelial progenitor cell
- FAH(−/−), fumarylacetoacetate hydrolase knockout mouse
- G-CSF, granulocyte-colony stimulating factor
- HCC, hepatocellular carcinoma
- HGF, hepatocyte growth factor
- HSC, haematopoietic stem cell
- HpSC, hepatic stellate cell
- MAPC, multipotent adult progenitor cell
- MMP-9, matrix metalloproteinase-9
- MSC, mesenchymal stem cell
- NOD/SCID, non-obese diabetes/severe combined immune deficiency
- SDF-1, stromal derived factor-1
Stem cells are present in a variety of organs including the bone marrow (BM). Their role is to replenish multiple mature differentiated cell types and thereby achieve long-term tissue reconstitution. Stem cells retain the capacity to generate progeny and renew themselves throughout life. Haematopoietic stem cells (HSCs) are the main stem cell population within the BM and give rise to all mature blood lineages via erythroid, myelomonocytic and lymphoid precursors. A second type of bone marrow stem cell (BMSC), the mesenchymal stem cell (MSC), forms stromal tissue and can give rise to cells of mesodermal origin.
A longstanding principle of cell biology has been that cell loss is reconstituted via stem cells resident within and specific to an organ. However, recent work suggests that this paradigm may not hold for all organs or all types of injury, and tissue damage may attract migratory stem cell populations, particularly those from the BM. This observation has caused considerable interest in the field of liver disease, where new strategies to restore hepatocyte number, augment liver function and counteract progressive organ fibrosis are required. This article will focus on the various relationships between BMSCs and liver disease. It will concentrate on the evidence from animal models and human studies that BMSCs may aid in the regeneration of liver cell populations and may also contribute to the pathogenesis of liver damage. It will discuss the potential to use BMSCs for therapeutic application and review the current status of clinical trials in patients with liver disorders.
BMSCS DO NOT CONTRIBUTE SIGNIFICANTLY TO HEPATIC PARENCHYMAL CELL REPOPULATION UNDER NORMAL CIRCUMSTANCES
The physiology of liver cell regeneration
The hepatic parenchyma is made up of hepatocytes and cholangiocytes. Unlike other organs such as the gut, liver cell mass is restored primarily through division of the majority of mature hepatocytes and not via a dedicated stem cell population. After a regenerative stimulus, such as a two-thirds partial hepatectomy, most …
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