Loss of p27Kip1 enhances the transplantation efficiency of hepatocytes transferred into diseased livers
Anthony N. Karnezis, Marina Dorokhov, Markus Grompe, Liang Zhu
Anthony N. Karnezis, Marina Dorokhov, Markus Grompe, Liang Zhu
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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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Figure 6

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Immunohistochemical analysis of host livers after transplantation. Liver...
Immunohistochemical analysis of host livers after transplantation. Liver sections from animals sacrificed at 1 month (a) and 2 months (b) after transplantation were processed for H&E staining, FAH immunostaining for transplanted cells, and TUNEL staining for apoptotic cells. The insert in TUNEL staining represents a wild-type liver treated with DNase I to serve as a positive control of TUNEL staining. All photographs were taken at ×200.