The study investigates whether hepatocytes and cholangiocytes can derive from bone marrow cells in humans, a process previously observed in animal models. Researchers analyzed archival autopsy and biopsy liver specimens from recipients of therapeutic bone marrow transplants and orthotopic liver transplants. Immunohistochemical staining with CAM5.2, specific for cytokeratins 8, 18, and 19, confirmed the presence of hepatocytes and cholangiocytes. Fluorescence in situ hybridization (FISH) for X and Y chromosomes identified Y-positive hepatocytes and cholangiocytes in male control liver tissue and all study specimens. Cell counts adjusted for partial sampling of nuclei showed that Y-positive hepatocytes and cholangiocytes engraftment ranged from 4% to 43% and 4% to 38%, respectively. The findings suggest that hepatocytes and cholangiocytes can be derived from extrahepatic circulating stem cells, likely of bone marrow origin, and this "transdifferentiation" can replenish large numbers of hepatic parenchymal cells. This indicates the existence of bipotent hepatic progenitor cells in humans, which may have therapeutic implications for liver regeneration and repair.The study investigates whether hepatocytes and cholangiocytes can derive from bone marrow cells in humans, a process previously observed in animal models. Researchers analyzed archival autopsy and biopsy liver specimens from recipients of therapeutic bone marrow transplants and orthotopic liver transplants. Immunohistochemical staining with CAM5.2, specific for cytokeratins 8, 18, and 19, confirmed the presence of hepatocytes and cholangiocytes. Fluorescence in situ hybridization (FISH) for X and Y chromosomes identified Y-positive hepatocytes and cholangiocytes in male control liver tissue and all study specimens. Cell counts adjusted for partial sampling of nuclei showed that Y-positive hepatocytes and cholangiocytes engraftment ranged from 4% to 43% and 4% to 38%, respectively. The findings suggest that hepatocytes and cholangiocytes can be derived from extrahepatic circulating stem cells, likely of bone marrow origin, and this "transdifferentiation" can replenish large numbers of hepatic parenchymal cells. This indicates the existence of bipotent hepatic progenitor cells in humans, which may have therapeutic implications for liver regeneration and repair.