Loss of p27Kip1 enhances the transplantation efficiency of hepatocytes transferred into diseased livers
Anthony N. Karnezis, … , Markus Grompe, Liang Zhu
Anthony N. Karnezis, … , Markus Grompe, Liang Zhu
Published August 1, 2001
Citation Information: J Clin Invest. 2001;108(3):383-390. https://doi.org/10.1172/JCI11933.
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Article

Loss of p27Kip1 enhances the transplantation efficiency of hepatocytes transferred into diseased livers

Abstract

p27Kip1 is an important regulator of cyclin-dependent kinases. Studies with p27 knockout mice have revealed abnormalities in proliferation and differentiation of multiple cell types. Here we show that primary hepatocytes isolated from livers of adult p27 knockout mice exhibit higher levels of DNA synthesis activity in culture than do wild-type cells. Interestingly, we found that, compared with control hepatocytes, p27 knockout hepatocytes proliferate better after transplantation into diseased livers to reverse liver failure. These results reveal an aspect of p27 that could be used to benefit cell-based therapy.

Authors

Anthony N. Karnezis, Marina Dorokhov, Markus Grompe, Liang Zhu

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Rescue of male FAH knockout mice by hepatocytes. (a) Kaplan-Meier surviv...
Rescue of male FAH knockout mice by hepatocytes. (a) Kaplan-Meier survival curve of FAH knockout mice after hepatocyte transplantation and withdrawal of NTBC treatment. The graph does not include animals that were excluded before their deaths or sacrificed (see text). The difference in the two curves is statistically significant (P = 0.0003). (b) Body weight measurements of transplanted animals. The results are from one pair of donors (wild-type and p27 knockout), each transplanted into eight hosts. Body weight at the time of transplantation is indicated as 100%. In this transplantation experiment, one animal in the wild-type hepatocyte group was sacrificed before its imminent death (square), and four generally healthy animals in the p27 knockout hepatocyte group (square, diamond, cross, and open circle) were sacrificed at 30 days for histological analysis. All the remaining animals in the wild-type hepatocyte group died before day 40, but survived to 2 months in knockout hepatocyte group. One animal in the knockout hepatocyte group (rectangle) survived without regaining body weight.