Stem Cells and Liver Disease

The liver is the largest internal organ in mammals and is essential to maintain normal physiological function of the body’s tissues and organs. There are several major causes of liver disease, including viral hepatitis, liver cancer, and cirrhosis, along with fatty liver disease. The liver is responsible for converting toxins into a form able to be removed from the body relatively safely, whether these are endogenous toxins (such as metabolites of hormones) or exogenous toxins (such as medical drugs, components of foodstuffs, and recreational drugs such as alcohol). The liver has incredible restorative capabilities but can become diseased when overloaded continually or when acute assault occurs, such as poisoning or physical trauma. Abnormalities of liver function also exist, such as alpha-1 antitrypsin deficiency which can cause both liver disease and emphysema.

Liver Disease Treatments

Chronic liver disease usually leads to liver cirrhosis and remains difficult to treat in many cases. Liver transplantation is the only currently effective therapy available to patients but with a limited number of donors, risks of surgical complication, possible immunological reaction, and the expense of treatment, these liver transplants are far from straightforward. Stem cell therapy is, therefore, an exciting prospect for treating liver disease using either donated bone marrow, umbilical cord blood stem cells, or patients’ own cells to facilitate organ regeneration. Researchers have discovered the potential for bone marrow-derived stem cells to differentiate into hepatocytes (liver cells), and there are a multitude of studies using these stem cells to treat liver disease currently underway. Several studies have also been completed which show improvements in liver function following stem cell transplants in a large proportion of cases offering hope for those on transplant waiting-lists.

Liver Stem Cells

Stem cells which appear to offer potential for aiding liver regeneration include hepatocytes, oval cells, haematopoietic and mesenchymal stem cells and induced pluripotent stem cells. Clinical trials have successfully used stem cell transplants in patients with acute liver failure, and chronic liver disease with end-stage cirrhosis. Liver precursor cells (oval cells) can proliferate rapidly, changing their cellular composition, and giving rise to both hepatocytes and cholangiocytes in order to replace damaged and lost cells and maintain liver homeostasis, as demonstrated in animal models of liver injury. Induced pluripotent stem cells are somatic cells harvested from the patient and differentiated into hepatocytes in vitro with a number of researchers investigating ways to facilitate improved rates of differentiation into these restorative cells (Kisseleva, et al, 2010).

Recent Stem Cell Research into Liver Cells

Researchers in Tokyo, have recently completed a study into the relative capacity of induced pluripotent stem cell-derived hepatocytes to produce the same coagulation factors and other liver-specific proteins as resident liver cells (Kasuda, et al, 2011). This is a particular concern where pre-differentiated hepatocytes are used in stem cell therapy as the regeneration of liver tissue with liver cells incapable of expressing liver-specific proteins would compromise overall health. The researchers looked at the gene expression profiles for coagulation-related markers in induced pluripotent stem cell-derived hepatocytes including fibrinogen, factors II, V, VII, VIII, IX, X, XI, XII, and XIIIβ, protein C, protein S, antithrombin, plasminogen, von Willebrand factor, and ADAMTS13. In comparison to undifferentiated iPS cells and haematopoietic-like embryoid bodies used as controls in the study, the hepatocytes showed strong expression of almost all of those genes related to the coagulation cascade making them look like ideal candidates for stem cell transplantation for liver disease.

Continue Reading –> Types of Stem Cells to Treat Liver Disease