Nature Medicine
6, 271 - 277 (2000)
doi:10.1038/73119
In vitro neurogenesis by progenitor cells isolated from the adult
human hippocampusNeeta Singh Roy1, Su Wang1, Li Jiang4, Jian Kang4, Abdellatif Benraiss1, Catherine Harrison-Restelli1, Richard A. R. Fraser2, William T. Couldwell3, Ayano Kawaguchi5, 6, Hideyuki Okano5, 6, Maiken Nedergaard3, 4
& Steven A. Goldman11
Departments of Neurology and Neuroscience, Cornell
University Medical College, 1300 York Ave. Room E607,
New York, New York 10021, USA
2
Department of Neurosurgery, Cornell University Medical
College, 1300 York Ave. Room E607, New York,
New York 10021, USA
3
Department of Neurosurgery, Valhalla,
New York 10585, USA
4
Department of Cell Biology, New York Medical College
, Valhalla, New York 10585, USA
5
Division of Neuroanatomy, Osaka University Graduate
School of Medicine, 2-2 Yamadaoka Suita, Osaka
, 565-0867 Japan
6
Core Research for Evolutional Science and Technology,
Japan Science and Technology Corporation, 2-2 Yamadaoka Suita
, Osaka, 565-0867 Japan
Correspondence should be addressed to Steven A. Goldman sgoldm@mail.med.cornell.eduNeurogenesis persists in the adult mammalian hippocampus. To identify and
isolate neuronal progenitor cells of the adult human hippocampus, we transfected
ventricular zone-free dissociates of surgically-excised dentate gyrus with
DNA encoding humanized green fluorescent protein (hGFP), placed under the
control of either the nestin enhancer (E/nestin) or the T 1 tubulin
promoter (P/T 1), two regulatory regions that direct transcription in
neural progenitor cells. The resultant P/T 1:hGFP+ and
E/nestin:enhanced (E)GFP+ cells expressed III-tubulin
or microtubule-associated protein-2; many incorporated bromodeoxyuridine,
indicating their genesis in vitro. Using fluorescence-activated cell
sorting, the E/nestin:EGFP+ and P/T 1:hGFP+
cells were isolated to near purity, and matured antigenically and physiologically
as neurons. Thus, the adult human hippocampus contains mitotically competent
neuronal progenitors that can be selectively extracted. The isolation of these
cells may provide a cellular substrate for re-populating the damaged or degenerated
adult hippocampus.
|