Donor-derived hepatocytes in human hematopoietic cell transplant recipients: evidence of fusion

AbstractReconstitution of hepatocytes by hematopoietic stem cells —a phenomenon which occurs in rodents under highly selective conditions—results from infrequent fusion between incoming myelomonocytes and host hepatocytes, with subsequent proliferation. Human hematopoietic stem cell transplant recipients have been little studied, with some support for transdif ferentiation (direct differentiation). We studied routinely obtained autopsy liver tissue of four female hematopoietic cell transplant recipients with male donors, using a highly specific conjoint immunohistochemistry in situ hybridization light microscopic technique. Hepatocyte nuclei were identifi ed by cytokeratin (Cam5.2) staining and evaluated for X and Y chromosome content. Over 1.6 million hepatocytes were assessed for rare instances of donor origin, revealing a Y chromosome in 67. Mixed tetraploids (XXXY) and their nuclear truncation products (XXY, XY, Y) were directly demonstrated, wit h no detection of the male tetraploids (XXYY) that may result from transdifferentiation with subsequent tetraploidization, nor their unique truncation products (XYY, YY), implicating fusion as the mechanism. To determine whether it is the sole mechanism, we modeled the chromosome distribution based on the same probability of detection of each X chromosome, deriving parameters of sensitivity and female tetraploidy by best fit. We then hypothesized that the distribution of Y chromosome–containing cells could be predicted by a...
Source: Virchows Archiv - Category: Pathology Source Type: research