In vivo haematopoietic potential of human neural stem cells.
The fetal sheep model was used to compare the in vivo haematopoietic potential of human neural stem cells (NSC) versus bone marrow (BM)-derived haematopoietic stem cells (HSC). To this end, sheep were transplanted with either 8 x 10(5) NSC (n = 11) or HSC, CD34(+)Lin(-) (n = 5), and subsequently analysed for haematopoietic chimaerism. While HSC-transplanted sheep displayed robust donor-derived haematopoiesis starting at less than 2 months post-transplant, NSC recipients exhibited haematopoietic engraftment at much later time points. Nevertheless, chimaerism persisted in both groups throughout the course of this study. Transplantation of secondary recipients with human CD45(+)/HLA-DR(+) cells from the BM of NSC primary recipients at 14 and 16 months post-transplant demonstrated that long-term engrafting HSC were present in these animals. At 6 months post-transplant, both NSC- and HSC-transplanted sheep were mobilised with granulocyte colony-stimulating factor. In contrast to HSC-transplanted animals, levels of human blood cells in peripheral blood of NSC-transplanted sheep remained low throughout mobilisation. Our results show that, although human NSC were able to give rise to multilineage haematopoiesis in our model, the levels, timing of blood cell production and the ability to respond to cytokine mobilisation were different, suggesting that human NSCs latent haematopoietic potential is inherently different from that of true HSC.
Almeida-Porada
G
G
Department of Animal Biotechnology, School of Veterinary Medicine and Department of Medicine, University of Nevada, Reno and VA Medical Center, Reno, NV, USA. galmeida@cabnr.unr.edu
Crapnell
K
K
Porada
C
C
Benoit
B
B
Nakauchi
H
H
Quesenberry
P
P
Zanjani
E D
ED
D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement / Q000187:drug effects; D016332:Fetal Tissue Transplantation; D006085:Graft Survival; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000032:analysis; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D009474:Neurons / Q000166:cytology / Q000637:transplantation*; D012756:Sheep; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology*; D018183:Transplantation Chimera
D006684:HLA-DR Antigens; D016179:Granulocyte Colony-Stimulating Factor; D017493:Leukocyte Common Antigens