The repopulation potential of hepatocyte populations differing in size and prior mitotic expansion

Ken Overturf, Muhsen Al-Dhalimy, Milton Finegold, Markus Grompe

Research output: Contribution to journalArticle

154 Scopus citations

Abstract

Recently the stem cell-like regenerative potential of adult liver cells was demonstrated by serial transplantation. This repopulation capacity could be useful for the treatment of genetic liver diseases by cell transplantation and/or expansion of genetically manipulated cells. However, previous experiments used unfractionated populations of liver cells, and therefore it remained undetermined whether all hepatocytes or only a subpopulation (stem cells) possessed this high regenerative ability. To address this question we used centrifugal elutriation to separate hepatocytes by cell density. Unexpectedly, small hepatocytes (16 μm) had lower repopulation capacity during the first round of transplantation when compared with both the medium- sized (21 μm) and large (27 μm) cells. We also compared the repopulation capacity of hepatocytes that had undergone different degrees of in vivo expansion. Previous cell division neither reduced nor increased the repopulation capacity of transplanted liver cells. Finally, retroviral tagging experiments demonstrated that liver-repopulating cells occur at a frequency of > 1:10,000. We conclude that short-term therapeutic liver repopulation does not require progenitor or stem cells.

Original languageEnglish (US)
Pages (from-to)2135-2143
Number of pages9
JournalAmerican Journal of Pathology
Volume155
Issue number6
DOIs
StatePublished - Dec 1999

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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