Hepatocytes and Epithelial Cells of Donor Origin in Recipients of Peripheral-Blood Stem Cells

Abstract

BACKGROUND: Bone marrow contains stem cells with the potential to differentiate into mature cells of various organs. We determined whether circulating stem cells have a similar potential. METHODS: Biopsy specimens from the liver, gastrointestinal tract, and skin were obtained from 12 patients who had undergone transplantation of hematopoietic stem cells from peripheral blood (11 patients) or bone marrow (1 patient). Six female patients had received transplants from a male donor. Five had received a sex-matched transplant, and one had received an autologous transplant. Hematopoietic stem-cell engraftment was verified by cytogenetic analysis or restriction-fragment--length polymorphism analysis. The biopsies were studied for the presence of donor-derived epithelial cells or hepatocytes with the use of fluorescence in situ hybridization of interphase nuclei and immunohistochemical staining for cytokeratin, CD45 (leukocyte common antigen), and a hepatocyte-specific antigen. RESULTS: All six recipients of sex-mismatched transplants showed evidence of complete hematopoietic donor chimerism. XY-positive epithelial cells or hepatocytes accounted for 0 to 7 percent of the cells in histologic sections of the biopsy specimens. These cells were detected in liver tissue as early as day 13 and in skin tissue as late as day 354 after the transplantation of peripheral-blood stem cells. The presence of donor cells in the biopsy specimens did not seem to depend on the intensity of tissue damage induced by graft-versus-host disease. CONCLUSIONS: Circulating stem cells can differentiate into mature hepatocytes and epithelial cells of the skin and gastrointestinal tract.