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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Quantitation of repopulation efficiencies. (a) Semi-quantitative PCR ana...
Quantitation of repopulation efficiencies. (a) Semi-quantitative PCR analysis of FAH genomic sequences. Primers for FAH mouse genotyping (10) were used in PCR on genomic DNA from livers of transplanted animals. In lanes 1–6, known amounts of wild-type and FAH knockout genomic DNA were premixed (the percentages of FAH wild-type donor DNA are indicated) for PCR to serve as reference points. The ratio of host/donor DNA bands was used to calculate repopulation percentages (see Methods) indicated under each animal (four mice for each genotype). (b) Western blot for FAH protein in transplanted livers as indicated. Similar to a, known amounts of extracts from wild-type and FAH knockout livers were mixed in lanes 1–6 at the indicated ratios. The four animals from each genotype were the same as those in a.