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Liver from bone marrow in humans.

N D Theise1, M Nimmakayalu, R Gardner

  • 1Department of Pathology, New York University, School of Medicine, New York, NY 10016, USA. Neil.Theise@med.nyu.edu

Hepatology (Baltimore, Md.)
|June 28, 2000
PubMed
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Human liver cells, including hepatocytes and cholangiocytes, can originate from circulating stem cells, likely from bone marrow. This transdifferentiation process can significantly replenish hepatic parenchymal cells.

Area of Science:

  • Hepatology
  • Stem Cell Biology
  • Transplantation Medicine

Background:

  • Animal models suggest bone marrow cells can differentiate into hepatocytes and cholangiocytes.
  • The occurrence of this transdifferentiation in humans remains to be elucidated.

Purpose of the Study:

  • To investigate whether hepatocytes and cholangiocytes in humans can derive from extrahepatic circulating stem cells, specifically of bone marrow origin.

Main Methods:

  • Utilized archival liver specimens from bone marrow and liver transplant recipients.
  • Employed immunohistochemical staining (CAM5.2) and fluorescence in situ hybridization (FISH) for X and Y chromosomes.
  • Quantified Y-positive hepatocytes and cholangiocytes to assess engraftment.

Main Results:

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  • Identified Y-positive hepatocytes and cholangiocytes in human liver specimens from male donors to female recipients.
  • Adjusted cell counts revealed significant engraftment, ranging from 4% to 43% for hepatocytes and 4% to 38% for cholangiocytes.
  • Peak engraftment observed in a liver transplant recipient with recurrent hepatitis C.

Conclusions:

  • Demonstrated that hepatocytes and cholangiocytes in humans can be derived from extrahepatic circulating stem cells.
  • This bone marrow-derived stem cell transdifferentiation can substantially replenish hepatic parenchymal cells.
  • Findings have implications for regenerative medicine and understanding liver repair mechanisms.