Liver from bone marrow in humans

It has been shown in animal models that hepatocytes and cholangiocytes can derive from bone marrow cells. We have investigated whether such a process occurs in humans. Archival autopsy and biopsy liver specimens were obtained from 2 female recipients of therapeutic bone marrow transplantations with male donors and from 4 male recipients of orthotopic liver transplantations from female donors, Immunohistochemical staining with monoclonal antibody CAM5.2, specific for cytokeratins 8, 18, and 19, gave typical strong staini ng of hepatocytes, cholangiocytes, and ductular reactions in all tissues, t o the exclusion of all nonepithelial cells. Slides were systematically phot ographed and then restained by fluorescence in situ hybridization (FISH) fo r X and Y chromosomes. Using morphologic criteria, field-by-field compariso n of the fluorescent images with the prior photomicrographs, and persistenc e of the diaminiobenzidene (DAB) stain through the FISH protease digestion, Y-positive hepatocytes and cholangiocytes could be identified in male cont rol liver tissue and in all study specimens. Cell counts were adjusted base d on the number of Y-positive cells in the male control liver to correct fo r partial sampling of nuclei in the 3-micron thin tissue sections. Adjusted Y-positive hepatocyte and cholangiocyte engraftment ranged from 4% to 43% and from 4% to 38%, respectively, in study specimens, with the peak values being found in a case of fibrosing cholestatic recurrent hepatitis C in one of the liver transplant recipients, We therefore show that in humans, hepa tocytes and cholangiocytes can be derived from extrahepatic circulating ste m cells, probably of bone marrow origin, and such "transdifferentiation" ca n replenish large numbers of hepatic parenchymal cells.