Identification of a candidate human neurohematopoietic stem-cell population.
It was recently reported that transplantation of clonally derived murine neurosphere cells into sublethally irradiated allogeneic hosts leads to a donor-derived hematopoietic reconstitution. The confirmation of the existence of a common neurohematopoietic stem cell in the human brain will have a significant effect on stem cell research and on clinical transplantation. Here, it is demonstrated that the human fetal brain contains separate but overlapping epidermal growth factor (EGF)-responsive and basic fibroblast growth factor (FGF-2)-responsive neural stem cells. The majority (> 85%) of cells within these EGF- and/or FGF-2-generated neurospheres express characteristic neural stem/progenitor cell markers including nestin, EGF receptor, and FGF-2 receptor. These neural stem cells can be continuously passaged in vitro, and demonstrate a constant 20-fold expansion in every passage for up to the fifth passage (the longest period that has been carried out in the authors' laboratory). These neural stem cells are multipotential for neurons, astrocytes, and oligodendrocytes. After transplantation into SCID-hu mice, all neural stem cells, regardless of passages, culture conditions, and donors, are able to establish long-term hematopoietic reconstitution in the presence of an intact human bone marrow microenvironment.
Shih
C C
CC
Division of Hematology/Bone Marrow Transplantation, City of Hope National Medical Center, City of Hope, Duarte, CA 91010-3000, USA. cshih@coh.org
Weng
Y
Y
Mamelak
A
A
LeBon
T
T
Hu
M C
MC
Forman
S J
SJ
D000029:Abortion, Legal; D001921:Brain / Q000166:cytology / Q000196:embryology*; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology; D003470:Culture Media; D004815:Epidermal Growth Factor / Q000032:analysis; D005260:Female; D005333:Fetus; D016222:Fibroblast Growth Factor 2 / Q000032:analysis; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D011247:Pregnancy; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology
D003470:Culture Media; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor