It was recently reported that transplantation of clonally derived murine ne
urosphere cells into sublethally irradiated allogeneic hosts leads to a don
or-derived hematopoietic reconstitution. The confirmation of the existence
of a common neurohematopoietic stem cell in the human brain will have a sig
nificant effect on stem cell research and on clinical transplantation. Here
, it is demonstrated that the human fetal brain contains separate but overl
apping 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 characterist
ic neural stem/progenitor cell markers including nestin, EGF receptor, and
FGF-2 receptor. These neural stem cells can be continuously passaged in vit
ro, 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 aut
hors' 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 dono
rs, are able to establish long-term hematopoietic reconstitution in the pre
sence of an intact human bone marrow microenvironment. (C) 2001 by The Amer
ican Society of Hematology.