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Blood, 15 October 2001, Vol. 98, No. 8, pp. 2412-2422
HEMATOPOIESIS
Identification of a candidate human neurohematopoietic
stem-cell population
Chu-Chih Shih,
Yehua Weng,
Adam Mamelak,
Thomas LeBon,
Mickey C.-T. Hu, and
Stephen J. Forman
From the Division of Hematology/Bone Marrow
Transplantation, and Division of Surgery, City of Hope National Medical
Center; Department of Molecular Biology, Beckman Research Institute at
the City of Hope; and Department of Professional Education, City of
Hope, Duarte, CA; and Department of Cell Biology, Amgen, Thousand Oaks,
CA.
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.
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