Direct isolation of human central nervous system stem cells.
Stem cells, which are clonogenic cells with self-renewal and multilineage differentiation properties, have the potential to replace or repair damaged tissue. We have directly isolated clonogenic human central nervous system stem cells (hCNS-SC) from fresh human fetal brain tissue, using antibodies to cell surface markers and fluorescence-activated cell sorting. These hCNS-SC are phenotypically 5F3 (CD133)(+), 5E12(+), CD34(-), CD45(-), and CD24(-/lo). Single CD133(+) CD34(-) CD45(-) sorted cells initiated neurosphere cultures, and the progeny of clonogenic cells could differentiate into both neurons and glial cells. Single cells from neurosphere cultures initiated from CD133(+) CD34(-) CD45(-) cells were again replated as single cells and were able to reestablish neurosphere cultures, demonstrating the self-renewal potential of this highly enriched population. Upon transplantation into brains of immunodeficient neonatal mice, the sorted/expanded hCNS-SC showed potent engraftment, proliferation, migration, and neural differentiation.
Uchida
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StemCells, Inc., 525 Del Rey Avenue, Suite C, Sunnyvale, CA 94085; Laboratory of Genetics, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. nichida@stemcell.net
Buck
D W
DW
He
D
D
Reitsma
M J
MJ
Masek
M
M
Phan
T V
TV
Tsukamoto
A S
AS
Gage
F H
FH
Weissman
I L
IL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D018952:Antigens, CD34 / Q000032:analysis; D015415:Biomarkers; D001921:Brain / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D051927:CD24 Antigen; D002454:Cell Differentiation; D002469:Cell Separation; D002490:Central Nervous System / Q000166:cytology*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D013116:Spinal Cord / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018952:Antigens, CD34; D015415:Biomarkers; D051927:CD24 Antigen; C497889:CD24 protein, human; C497890:Cd24a protein, mouse; D008562:Membrane Glycoproteins; D017493:Leukocyte Common Antigens