To investigate multitissue engraftment of human primitive hematopoietic cells and their differentiation in goats, human CD34 ؉ Lin ؊ cord blood cells transduced with a GFP vector were transplanted into fetal goats at 45-55 days of gestation. GFP ؉ cells were detected in hematopoietic and nonhematopoietic organs including blood, bone marrow, spleen, liver, kidney, muscle, lung, and heart of the recipient goats (1.2-36% of all cells examined). We identified human 2 microglobulin-positive cells in multiple tissues. GFP ؉ cells sorted from the perfused liver of a transplant goat showed human insulin-like growth factor 1 gene sequences, indicating that the engrafted GFP ؉ cells were of human origin. A substantial fraction of cells engrafted in goat livers expressed the human hepatocyte-specific antigen, proliferating cell nuclear antigen, albumin, hepatocyte nuclear factor, and GFP. DNA content analysis showed no evidence for cellular fusion. Long-term engraftment of GFP ؉ cells could be detected in the blood of goats for up to 2 yr. Microarray analysis indicated that human genes from a variety of functional categories were expressed in chimeric livers and blood. The human͞goat xenotransplant model provides a unique system to study the kinetics of hematopoietic stem cell engraftment, gene expression, and possible stem cell plasticity under noninjured conditions. hematopoietic stem cell ͉ transplantation ͉ plasticity ͉ microarray
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