Multiorgan engraftment and differentiation of human cord blood CD34+ Lin- cells in goats assessed by gene expression profiling.
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 beta2 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.
Zeng
Fanyi
F
Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University, 24/1400 West Beijing Road, Shanghai 200040, People's Republic of China. ytzeng@stn.sh.cn
Chen
Mei-jue
MJ
Baldwin
Don A
DA
Gong
Zhi-juan
ZJ
Yan
Jing-bin
JB
Qian
Hui
H
Wang
Juan
J
Jiang
Xiaoyan
X
Ren
Zhao-rui
ZR
Sun
Deming
D
Huang
Shu-zhen
SZ