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Multiorgan engraftment and differentiation of human cord blood CD34+Lin- cells in goats assessed by gene expression profiling
被引:37
作者:
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
机构:
[1] Shanghai Jiao Tong Univ, Shanghai Childrens Hosp, Inst Med Genet, Shanghai 200040, Peoples R China
[2] Univ Penn, Penn Microarray Facil, Philadelphia, PA 19104 USA
[3] Univ British Columbia, British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada
[4] Univ British Columbia, Dept Med Genet, Vancouver, BC V5Z 1L3, Canada
来源:
关键词:
hematopoietic stem cell;
transplantation;
plasticity;
microarray;
D O I:
10.1073/pnas.0602646103
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
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 beta 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 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.
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页码:7801 / 7806
页数:6
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