Thesis live: 1.2 Liver, regeneration and stem/progenitor cells

In the live thesis building blogxperiment I edit (digest, compile, write, rewrite, delete) my ongoing doctoral thesis in blog posts and put the parts together on thesis live. The title: The physiologic role of stem cells in tissues with different regenerative potential.

1.2. Tissues, organs with different turnover and regenerative potential

/bioenergetics data missing/

Liver

During organogenesis the hepatic endoderm epithelium invades the surrounding mesenchyme to form the liver bud and continued epithelial/mesenchymal interactions stimulate cell proliferation and morphogenesis. Consequently, the liver is largely of endodermal origin – including cells with a mesodermal origin and – and contains many different cell types: two epithelial liver cell types, the hepatocytes and bile duct cells, stellate cells (formerly called Ito cells), Kupffer cells, vascular endothelium, fibroblasts, and leukocytes (Desmet 1994). Hepatocytes are the main funtional liver cells accounting for ~70% of the cells in the liver and form the bulk of the liver weight (90%), yet only ~60% of total liver DNA is hepatocyte-derived (many of them with 2n, 4n, 8n DNA content). An adult human liver contains about 80 x10(9), hepatocytes. Hepatocytes are in a quiescent state and the turnover rate is low, 1-2 times/year[]. The remarkable regenerative potential of liver is well-known, in humans the liver almost completely regenerates in about 1 month after two-thirds (up to 75%) partial hepatectomy and this process can occur repeatedly in contrast to most other parenchymal organs, such as kidney or pancreas. In the literature the term liver or hepatic stem cells is used for precursors of the hepatocytes and the bile duct epithelial cells. On the other hand liver stem/progenitor cells can be define in different ways. The cells which give rise to regeneration after partial hepatectomy and in other liver injuries are differentiated hepatocytes with a virtually unlimited differentiation potential. This type of endogenous liver regeneration is progenitor independent. Transplanted hepatocytes also have the ability to repopulate damaged, injured recipient livers [Rhim et al 1994.] but the hepatocytes do not significantly repopulate normal adult liver following transplantation. Although unique liver stem cell markers are not currently available, “oval cells” are the best candidates for non-hepatocyte, progenitor-dependent liver regeneration. These cells have a high nuclear/cytoplasmic ratio, termed oval cells due to the initial morphology and their parent cells probably reside in the canal of Hering. Oval cells express markers of both bile duct epithelium (CK-7, CK19, OV-6) and hepatocytes (albumin, alpha-fetoprotein) and are bipotential; have the ability to differentiate into both of the major liver cell types (Sirica et al. 1990; Sirica 1995). Oval cells also express also express hematopoietic stem cell (HSC) genes (c-kit, CD34, Sca-1 and Thy-1) however the idea that hematopoietic stem cells in the bone marrow are the ancestors of oval cells seems improbable and several recent studies in mice and rats have shown that transdifferentiation of HCS into “oval cells” is a very rare event probably without physiological significance [Thorgeirsson S, Grisham J 2006]. Oval cells are facultative liver stem cells that is in case of specific chronic injuries, caused by chemicals such as DL-ethionine, galactosamine, and azo dyes they regenerate the liver in murine models.

Literature:

Thorgeirsson S,Grisham J. (2006) Hematopoietic cells as liver epithelial stem cells: a critical review of all the evidence, Hepatology 43 2–11.
http://www.cincinnatichildrens.org/research/div/dev-biology/fac-labs/zorn-lab/liver-dev.htm
Grompe M, Finegold MJ (2001) Liver Stem Cells Stem Cell Biology 455-497 Cold Spring Harbor Laboratory Press
Oertel M, Shafritz DA. Stem cells, cell transplantation and liver repopulation Biochim Biophys Acta. 2008 Feb;1782(2):61-74.
Rhim JA, Sandgren EP, Degen JL, Palmiter RD, Brinster RL. (1994) Replacement of diseased mouse liver by hepatic cell transplantation. Science. 263(5150):1149-52.

2 thoughts on “Thesis live: 1.2 Liver, regeneration and stem/progenitor cells

  1. Ah, you’re talking about something I know a little about. Liver is indeed a well studied model of regeneration, but it’s also a prime model for studying cancer stem cells, as it has been found that different modes of injury lead to a regenerative response involving different subsets of liver progenitors. Ductal progenitor cells and Oval cells and hepatocytes all contribute to repair, but the interesting thing is that chronic injury and chronic stimulation of cell division for repair, often leads to tumor development, with the prognosis of the cancer becoming more serious as the contribution from less differentiated cells increases.

    So, realistically, the idea of unlimited regenerative potential is limited by the onset of malignancy.

  2. OK,
    I found out about your PhD blogxperiment via Jean-Claude Bradley and I’m interested.
    – subscribed to yr RSS
    – here for your encouragement
    (I know nothing about your research but am three years into a journey of self-education via all this read/write web stuff – working as new media consultant to the University of Adelaide to pay the bills).

    Hang in there and keep up the great work.
    Fang – Mike Seyfang

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