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Proliferation of Transplanted Hepatocytes Drives Efficient Repopulation in Juvenile Host Rat Livers
Author(s) -
Stock Peggy,
Hempel Madlen,
Hsu MeiJu,
Christ Bruno
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.531.11
Subject(s) - juvenile , hepatocyte , transplantation , biology , flow cytometry , parenchyma , andrology , cell , immunology , medicine , in vitro , biochemistry , genetics , botany
To improve the engraftment of donor hepatocytes is a central goal to enhance the therapeutic efficacy of hepatocyte transplantation as an alternative to whole liver transplantation. We reported previously that efficient liver repopulation by transplanted hepatocytes was hampered in livers of old as compared to juvenile animals 6 weeks after transplantation. To investigate, whether this was due to a better initial entry into the host parenchyma of juvenile as compared to senescent donor cells, or to differences in proliferation, we determined repopulation rates in juvenile and senescent host livers 1 week after transplantation of juvenile and senescent hepatocytes by flow cytometry and quantification of DPPIV enzyme activity in liver sections. Proliferation was assessed in the liver parenchyma by the expression of Ki67 six weeks after cell transplantation. 1 week after hepatocyte transplantation comparable numbers of scattered cell clusters appeared both in juvenile and senescent host livers, irrespective of the age of the donor hepatocytes. However, quantification by flow cytometry of isolated primary hepatocytes from these livers revealed significantly higher numbers of juvenile as compared to senescent transplanted hepatocytes in juvenile hosts and as compared to either cell type in senescent host livers. This indicates that no differences in the parenchymal entry were obvious but rather higher proliferation of juvenile hepatocytes for higher numbers of transplanted cells in the juvenile host livers. Indeed, 6 weeks after hepatocyte transplantation significantly higher proliferation rates of transplanted hepatocytes were observed in juvenile host livers (4.2%) as compared to senescent hosts (zero), respectively. Hence, irrespective of the age of donor hepatocytes the parenchymal entry is similar but the efficient repopulation by juvenile hepatocytes seemed to rely on higher proliferation rates during liver regeneration.