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Cited by 156Liver physiology and pathologyOrgan Transplantation Techniques and OutcomesTissue Engineering and Regenerative Medicine

To divide or not to divide: revisiting liver regeneration

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Miyaoka, Yuichiro, Miyajima, Atsushi·2013·Cell Division
DOI 10.1186/1747-1028-8-8PMC PMC3695844
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Abstract

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.

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  • The Akt/mTORC1 pathway is a key mediator of cell growth in many cellular systems, including certain settings of liver regeneration.

    “However, The Akt/mTORC1 pathway is a key mediator of cell growth in many cellular systems, including certain settings of liver regeneration[55].”

    From Liver regeneration after partial hepatectomy: Triggers and mechanisms (2025) · cites this paper as [55]

    In “Hepatocytes enlarge” (page unavailable), the paper says the Akt–mTOR axis regulates the size of various cell types and seems important for hepatocyte hypertrophy during liver regeneration. It discusses mTOR generally, however, and does not identify mTORC1 specifically as the mediator. (LLM, conf=0.79)

    Experimental — accuracy not yet measured

  • Hyperplasia and hypertrophy do not equally affect all hepatocytes and all lobes after partial hepatectomy.

    “However, in the same study, Miyaoka and Miyajima note that the process of hyperplasia and hypertrophy does not equally affect all hepatocytes and all lobes.”

    From Liver regeneration after partial hepatectomy: Triggers and mechanisms (2025) · cites this paper as [55]

    In the Introduction’s “A revised model of liver regeneration” (page unavailable), the paper says not all hepatocytes divide after partial hepatectomy, supporting unequal participation in hyperplasia. But Figure 5 says all hepatocytes enlarge, and the cited passages do not establish that hypertrophy or hyperplasia differs among the remaining lobes. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Binucleated hepatocytes are commonly detected during liver regeneration, and their presence reflects ongoing mitotic activity not followed by cytokinesis.

    “In addition, binucleated hepatocytes are commonly detected during liver regeneration. Their presence reflects ongoing mitotic activity that is not followed by cytokinesis.”

    From Liver regeneration after partial hepatectomy: Triggers and mechanisms (2025) · cites this paper as [55]

    The section “Cell division of binuclear hepatocytes to produce mononuclear cells” confirms that binuclear hepatocytes are observed during regeneration. But it says their number decreases during regeneration and describes incomplete cytokinesis as a cause of binucleation during liver maturation, not as what their presence indicates during regeneration. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Hepatocytes undergo not only hyperplasia but also hypertrophy during liver regeneration.

    “These data prove that hepatocytes undergo not only hyperplasia but also the hypertrophy, which during their proliferation is carried out by the pathway[55].”

    From Liver regeneration after partial hepatectomy: Triggers and mechanisms (2025) · cites this paper as [55]

  • After 70% hepatectomy, the number of hepatocytes in the remaining lobes increases 1.6 times and the mass of these lobes increases 2.4 times.

    “According to Miyaoka and Miyajima's calculations[55], the number of hepatocytes in the remaining lobes after 70% hepatectomy increases 1.6 times, and the mass of these lobes increases 2.4 times.”

    From Liver regeneration after partial hepatectomy: Triggers and mechanisms (2025) · cites this paper as [55]

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References 122 · Cited by 156

Research works printed but not linked: 107

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Authors
Miyaoka, Y., & Miyajima, A.
Affiliations
  • University of California, San Francisco (US)
  • The University of Tokyo (JP)
Corresponding author
Miyajima, Atsushi
ORCID
Venue
Cell Division
Publisher
Springer Science and Business Media LLC
Published
2013
Volume
8
Issue
1
Pages
8
ISSN
1747-1028 (ISSN-L)
DOI
10.1186/1747-1028-8-8
PMC
PMC3695844
OpenAlex
W2166192049
Cited by
156
References
122
Citations by year
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FWCI
7.89
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Cell Division (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Ministry of Education, Culture, Sports, Science and Technology (CREST)
  • Ministry of Health, Labour and Welfare
  • Japan Society for the Promotion of Science (CREST)
  • Japan Science and Technology Agency (CREST)
  • Core Research for Evolutional Science and Technology
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
liver regeneration, partial hepatectomy, hepatocyte proliferation, binuclear hepatocytes, hepatocyte size, DNA replication, nuclear number

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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