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Am J Physiol Gastrointest Liver Physiol 276: G1260-G1272, 1999;
0193-1857/99 $5.00
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Vol. 276, Issue 5, G1260-G1272, May 1999

Partial hepatectomy-induced polyploidy attenuates hepatocyte replication and activates cell aging events

Samuel H. Sigal1,3, Pankaj Rajvanshi1,3, Giridhar R. Gorla1,4, Rana P. Sokhi1,3, Romil Saxena5, David R. Gebhard Jr.2, Lola M. Reid1,2,6,7, and Sanjeev Gupta1,2,3

1 Marion Bessin Liver Research Center, 2 Cancer Research Center, and Departments of 3 Medicine, 4 Radiation Oncology, 5 Pathology, and 6 Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461; and 7 Center for Gastrointestinal and Biliary Disease Studies and Program in Molecular Biology and Biotechnology, University of North Carolina School of Medicine at Chapel Hill, Chapel Hill, North Carolina 27514

In understanding mechanisms of liver repopulation with transplanted hepatocytes, we studied the consequences of hepatic polyploidization in the two-thirds partial hepatectomy model of liver regeneration. Liver repopulation studies using genetically marked rodent hepatocytes showed that the number of previously transplanted hepatocytes did not increase in the liver with subsequential partial hepatectomy. In contrast, recipients undergoing partial hepatectomy before cells were transplanted showed proliferation in transplanted hepatocytes, with kinetics of DNA synthesis differing in transplanted and host hepatocytes. Also, partial hepatectomy caused multiple changes in the rat liver, including accumulation of polyploid hepatocytes along with prolonged depletion of diploid hepatocytes, as well as increased senescence-associated beta -galactosidase and p21 expression. Remnant hepatocytes in the partially hepatectomized liver showed increased autofluorescence and cytoplasmic complexity on flow cytometry, which are associated with lipofuscin accumulation during cell aging, and underwent apoptosis more frequently. Moreover, hepatocytes from the partially hepatectomized liver showed attenuated proliferative capacity in cell culture. These findings were compatible with decreased proliferative potential of hepatocytes experiencing partial hepatectomy compared with hepatocytes from the unperturbed liver. Attenuation of proliferative capacity and other changes in hepatocytes experiencing partial hepatectomy offer novel perspectives concerning liver regeneration in the context of cell ploidy.

liver; ploidy; apoptosis; hepatocyte transplantation


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