Recent studies have shown that primitive stem cells can mobilize and differentiate into hepatocytes. We investigated the time and extent in which cells of recipient origins could differentiate into hepatocytes and other cells in human liver allografts. Microsatellite analysis, which can assess quantitatively the proportions of recipient and donor DNA, was performed in posttransplantation liver biopsy specimens from 17 patients at various times. Combined fluorescence in situ hybridization (FISH) for Y chromosome and immunofluorescence for different cell types was also performed in 10 of these cases with sex mismatch.
Organ chimerism in the transplanted livers was found to be of variable extent, and the recipients' DNA in the posttransplantation liver biopsy specimens (excluding portal tracts) amounted up to 50%. The recipient DNA in the posttransplantation liver biopsy specimens increased after liver transplantation by as early as 1 week, peaked at around 30 to 40 weeks, and could be shown 63 weeks after transplantation. Most (64%-75%) of the recipientderived cells showed macrophage/Kupffer cell differentiation. Only up to l.6% of the recipient-derived cells in the liver grafts showed hepatocytic differentiation in the liver grafts and made up 0.62% of all hepatocytes of both donor and recipient origins. These livers had mild or minimal injury histologically. In conclusion, our results show that most of the recipient-derived cells in the liver allografts were macrophages/Kupffer cells and only a small proportion of hepatocytes was recipient derived. However, with regard to recipient-derived hepatocytes, our data cannot distinguish between transdifferentiation and cell fusion. (HEPATOLOGY 2003;38:989-998.) See Editorial on Page 804 ecent studies have shown that primitive stem cells can mobilize and may differentiate into hepato-R cytesl-5 and into other cells including cardiac muscle
neurons,8 and endothelial cells. In humans, liver transplantation provides an excellent system to study the cell migration from the host to the transplanted liver (organ chimerism). Such a form of chimerism might generate functional hepatocytes in the liver and sustain liver function, but the origin and fate of recipient Abbreviations: PCR, polymerase chain reaction; FISH, Juorescence in situ by-From the 'Department of Pathology, iClinical Trial Center,