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Open Access Highly Accessed Review

To divide or not to divide: revisiting liver regeneration

Yuichiro Miyaoka2 and Atsushi Miyajima1*

Author Affiliations

1 Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan

2 Current address: Gladstone Institute of Cardiovascular Disease, University of California at San Francisco, San Francisco, CA 94158, USA

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Cell Division 2013, 8:8  doi:10.1186/1747-1028-8-8

Published: 20 June 2013


The liver has a remarkable capacity to regenerate. Even with surgical removal (partial hepatectomy) of 70% of liver mass, the remnant tissue grows to recover the original mass and functions. Liver regeneration after partial hepatectomy has been studied extensively since the 19th century, establishing the long-standing model that hepatocytes, which account for most of the liver weight, proliferate to recover the original mass of the liver. The basis of this model is the fact that almost all hepatocytes undergo S phase, as shown by the incorporation of radioactive nucleotides during liver regeneration. However, DNA replication does not necessarily indicate the execution of cell division, and a possible change in hepatocyte size is not considered in the model. In addition, as 15–30% of hepatocytes in adult liver are binuclear, the difference in nuclear number may affect the mode of cell division during regeneration. Thus, the traditional model seems to be oversimplified. Recently, we developed new techniques to investigate the process of liver regeneration, and revealed interesting features of hepatocytes. In this review, we first provide a historical overview of how the widely accepted model of liver regeneration was established and then discuss some overlooked observations together with our recent findings. Finally, we describe the revised model and perspectives on liver regeneration research.

Akt; Cdks; Cellular hypertrophy; Cyclins; E2F family; Hepatocyte; Liver regeneration; mTOR; Partial hepatectomy; Polyploidy