Multiorgan engraftment and differentiation of human cord blood CD34 super(+)Lin super(-) cells in goats assessed by gene expression profiling

• Published in: Proceedings of the National Academy of Sciences - PNAS 2006-05, Vol.103 (20), p.7801-7806
• Main Authors: Zeng, Fanyi, Chen, Mei-Jue, Baldwin, Don A, Gong, Zhi-Juan, Yan, Jing-Bin, Qian, Hui, Wang, Juan, Jiang, Xiaoyan, Ren, Zhao-Rui, Sun, Deming, Huang, Shu-Zhen
• Format: Article
• Language: English
• ISSN: 0027-8424; 1091-6490

To investigate multitissue engraftment of human primitive hematopoietic cells and their differentiation in goats, human CD34 super(+)Lin super(-) cord blood cells transduced with a GFP vector were transplanted into fetal goats at 45-55 days of gestation. GFP super(+) 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 beta 2 microglobulin-positive cells in multiple tissues. GFP super(+) cells sorted from the perfused liver of a transplant goat showed human insulin-like growth factor 1 gene sequences, indicating that the engrafted GFP super(+) 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 super(+) 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.