1. Multiorgan engraftment and differentiation of human cord blood CD34+ Lin- cells in goats assessed by gene expression profiling
- Author
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Zhao-Rui Ren, Fanyi Zeng, Jing-Bin Yan, Shu-Zhen Huang, Xiaoyan Jiang, Juan Wang, Zhijuan Gong, Don A. Baldwin, Deming Sun, Mei-Jue Chen, and Hui Qian
- Subjects
Male ,Cellular differentiation ,Green Fluorescent Proteins ,Transplantation, Heterologous ,CD34 ,Antigens, CD34 ,Cord Blood Stem Cell Transplantation ,Biology ,Pregnancy ,medicine ,Animals ,Humans ,Tissue Distribution ,Oligonucleotide Array Sequence Analysis ,Transplantation Chimera ,Multidisciplinary ,Gene Expression Profiling ,Goats ,Hematopoietic stem cell ,Cell Differentiation ,Biological Sciences ,Hematopoietic Stem Cells ,Molecular biology ,Haematopoiesis ,medicine.anatomical_structure ,Liver ,Cord blood ,RNA ,Female ,Bone marrow ,Stem cell - Abstract
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 β2 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 human/goat 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.
- Published
- 2006