The human-sheep chimeras as a model for human stem cell mobilization and evaluation of hematopoietic grafts' potential.
OBJECTIVE
To investigate whether the sheep xenograft model of human hematopoiesis can be used to mimic mobilization of human hematopoietic stem cells in vivo.


METHODS
Sheep transplanted with 3.6 x 10(6) CD34+ from human adult bone marrow were mobilized 1.5 years posttransplantation with human granulocyte colony-stimulating factor for 5 days. At day 3 and 4 of mobilization, human cells were harvested from peripheral blood (PB) and bone marrow (BM) and were injected into secondary sheep recipients (n = 6) and these animals were analyzed for the presence of human cells in their BM and PB, starting at 3.5 months posttransplantation.


RESULTS
Maximum mobilization of human cells in PB occurred at day 3, with a 21-fold increase in total numbers of human cells, and a recovery of 5.5 x 10(4)/mL CD34+. In the BM, maximal numbers of human cells were achieved at day 4, with a 6.3-fold increase and a recovery of 1.5 x 10(4)/mL CD34+ cells. PB and BM mobilized human cells were then transplanted into new sheep recipients, and analysis at 3.5 months posttransplantation demonstrated that levels of human cell engraftment in BM of the group transplanted with mobilized PB were significantly lower than those transplanted with BM cells (0.6% +/- 0.1% vs 8.0% +/- 1.8%). Furthermore, in sheep transplanted with mobilized PB, the levels of human cells in circulation remained 2.5-fold higher than the levels of human cells found in their BM.


CONCLUSIONS
Mobilization of human cells in the sheep model parallels human PB and BM hematopoietic stem cells (HSC) mobilization in healthy human donors in their ability to engraft, differentiate, and repopulate secondary hosts. Thus, this model can become a useful tool to study mobilization regimens, mechanisms, and quality of products obtained.
Almeida-Porada
Graça
G
Department of Animal Biotechnology University of Nevada, Reno, NV 89557-0104, USA. galmeida@cabnr.unr.edu
Porada
Christopher
C
Gupta
Nicole
N
Torabi
Ali
A
Thain
David
D
Zanjani
Esmail D
ED
D000818:Animals; D018952:Antigens, CD34; D001853:Bone Marrow; D016026:Bone Marrow Transplantation; D005260:Female; D006085:Graft Survival; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D008954:Models, Biological; D011247:Pregnancy; D012756:Sheep; D013997:Time Factors; D018183:Transplantation Chimera; D014183:Transplantation, Heterologous
D018952:Antigens, CD34; D016178:Granulocyte-Macrophage Colony-Stimulating Factor