Endocrine Abstracts (2007) 13 S12

Pancreatic trans-differentiation and the treatment of liver damage

Karen Wallace1, Carylyn Marek2 & Matthew Wright1

1Newcastle University, Newcastle, United Kingdom; 2University of Aberdeen, Aberdeen, United Kingdom.

The liver performs essential functions including the control of blood nutrient levels; the synthesis of many blood proteins; the metabolism of bile components and the conversion of ammonia to urea for excretion by the kidney. Impaired urea synthesis is often the cause of coma and death in patients with liver failure. The only treatment for liver failure at present is transplantation.

Stem cells may be a promising future resource for the treatment of acute and chronic liver disease. Stems cells could be used to generate hepatocytes (the main functional cell of the liver) to populate an extra-corporeal device. The device could bridge liver function until a patient’s acutely damaged liver had recovered (the liver is unusual in that it may regenerate after extensive damage). Alternatively, stem cells - or hepatocytes derived therefrom - could be directly transplanted into a patient’s diseased liver. Recent research has demonstrated that embryonic stem cells, cells from cord blood, bone marrow and the pancreas have the ability to differentiate into hepatocyte-like cells under the appropriate conditions.

The rat AR42J-B13 cell is a pancreatic progenitor cell line that trans-differentiates into hepatocyte-like cells when exposed to glucocorticoids. Treatment with factors known to direct embryonic pancreatic cells into hepatocytes does not stimulate a trans-differentiation of AR42J-B13 cells into hepatocytes. Therefore, to determine if a pancreatic progenitor trans-differentiation to hepatocyte is a normal response to glucocorticoid, glucocorticoid was administered to adult rats for up to 25 days. Glucocorticoid treatment resulted in the presence of hepatocyte-like cells within the acinar region of the adult pancreas. Using a cell surface marker identified in the AR42J-B13 cell, glucocorticoid treatment was also seen to reduce the numbers of a probable related progenitor cell located within the periportal regions of the liver.

Progenitor cells for hepatocytes therefore exist in the pancreas and liver and glucocorticoid treatment is likely to be a feature of any successful progenitor – hepatocyte differentiation protocol.

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