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Adult liver stem cells: bone marrow, blood, or liver derived?
  1. H A CROSBY,
  1. School of Biosciences, University of Birmingham
  2. and Liver and Hepatobiliary Unit, University Hospital
  3. Birmingham, UK
  1. Professor A J Strain, Liver Research Labs, Queen Elizabeth Hospital, Edgbaston, Birmingham, B15 2TH, UK. a.j.strain{at}

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Another striking development has recently been made in the hepatic stem cell debate,1 with the publication of the two reports highlighted above. Since the appearance of papers demonstrating the potential of haematopoietic stem cells to “transdifferentiate” into liver epithelium in two different rodent bone marrow transplant models,2 ,3 several questions have been posed. For example, are all liver stem cells derived from a common haematopoietic precursor or are oval cells, now widely accepted as having bipotentiality1 (that is, the ability to differentiate into either hepatocytes or biliary epithelial cells (BEC)), present in the liver throughout development and into adulthood? Does this transdifferentiation process represent a pathophysiologically significant phenomenon and if so does it occur in humans? Does the effect depend on the degree of liver damage inflicted?

In both studies,4 ,5 two groups of patients were examined; female bone marrow transplant (bmtx) recipients receiving male donor cells and males transplanted with female donor livers. The fate of the donor marrow derived cells in the former and the host haematopoietic stem cells in the latter were followed by identifying male derived cells in histological sections of livers using molecular probes specific for the Y chromosome. In parallel, phenotypic markers were used to confirm that the haematopoietic cells were indeed differentiating into either hepatocytes or BEC. In the first study liver biopsies were examined from two bmtx and four liver transplant cases.4 In most cases a mild inflammatory reaction was reported in the livers. In the second,5 samples were from 11 males whose transplanted livers were later removed because of recurrent disease, and from nine bmtx patients, although little detail of the liver pathology (that is, degree, if any, of …

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