The possibility of pancreatic cells transdifferentiation into hepatoсyte-like cells in copper-deficient model of injury in rats was shown by M.S.Rao and D.G.Scarpelli (1981). Considering that hepatic stellate cells (HSC) play an important role in hepatocytes’ differentiation as well as common features of hepatic and pancreatic stellate cells (PSC) the aim of our work was to study HSC and PSC in rat copper-deficient model of injury
24 white Wistar male rats were maintained on copper-deficient diet (MP Biomedicals, USA) containing copper-chelating agent, triethylenetetramine tetrahydrochloride, for 8 weeks, and then were returned to normal rat chow for another 8 weeks. Groups of 3 animals each were killed after 2, 4, 6, and 8 weeks of diet and 2, 4, 6, and 8 weeks of recovery phase. Liver and pancreas paraffin sections were stained immunohistochemically with antibodies to desmin and alpha-smooth muscle actin (a-SMA) as well as by Mallory staining to detect connective tissue compounds in liver.
We observed increased number of desmin-positive HSC in periportal areas of liver (up to 20 cells per one portal tract) at all weeks of copper-deficient diet as well as from 5 to 15 cells per one central vein in pericentral areas from 4th to 8th week of diet. Single a-SMA-positive myofibroblasts were found in periportal areas at all weeks of copper-deficient diet with maximum a-SMA expression detected after 6 weeks of diet. After 8 weeks of diet only few a-SMA-positive cells were observed. Single desmin- and a-SMA-positive cells were found in liver parenchyma after rats were transferred to normal rat chow.
The Mallory staining revealed connective tissue fibers mainly in periportal areas with few porto-portal septa till the 6th week of copper-deficient diet. After rats were transferred to normal rat chow the amount of connective tissue decreased and reached the control levels by the end of the experiment.
The number of desmin-positive PSC in pancreatic acinar tissue and on periphery of islets increased by 6th week of diet and further increased till the 8th week of diet. After rats were transferred to normal rat chow the number of PSC decreased, and few desmin-positive cells were found in islets and along the border of remaining islets and newly formed acinar tissue.
Staining of pancreatic sections with antibodies to a-SMA revealed only smooth muscle cells of blood vessels during the whole experiment.
Conclusion: PSC and islet cells (possibly glucagon-producing cells as it was shown earlier in our lab) can be involved in pancreas regeneration including possible transdifferentiation into the hepatocyte-like cells in case of copper-deficient diet. The same pattern of changes in liver can be due to HSC response to liver injury reflecting common ways of pancreas and liver regeneration in copper-deficient model of injury.
