Brain transplantation of immortalized human neural stem cells promotes functional recovery

Lee HJ et al. Brain transplantation of immortalized human neural stem cells promotes functional recovery in mouse intracerebral hemorrhage stroke model. Stem Cells. 2007 Jan 18; [Epub ahead of print]

 

Brain Disease Research Center, Ajou University School of Medicine, Suwon, Korea; Department of Animal Science, Korea University, Seoul, Korea; Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver, Canada.

We have generated stable, immortalized cell lines of human neural stem cells (NSC) from primary human fetal telencephalon cultures via a retroviral vector encoding v-myc. HB1.F3, one of the human NSC lines, express normal human karyotype of 46,XX and nestin, a cell type-specific marker for NSC. F3 has the ability to proliferate continuously, and differentiate into cells of neuronal and glial lineage. HB1.F3 human NSC line was used for cell therapy in mouse model of intracerebral hemorrhage (ICH) stroke. Experimental ICH was induced in adult mice by intrastriatal administration of bacterial collagenase; one week after surgery, the mice were randomly divided into 3 groups so as to receive intracerebrally either F3 human NSCs labeled with beta-galactosidase (n=31), killed F3 NSCs (n= 21) or PBS (n=30). Transplanted NSCs were detected by X-gal histochemistry or double labeling with beta-gal and MAP2, neurofilaments (both for neurons) or GFAP (for astrocytes). Behavior of the animals was evaluated for period up to 8 weeks using modified rotarod tests and limb placement test. Transplanted human NSCs were identified in the peri-hematomal areas and differentiated into neurons (beta-gal/ MAP2+ and beta-gal/ NF+) or astrocytes (beta-gal / GFAP+). The NSC transplanted group showed markedly improved functional performance on rotarod test and limb placement after 2-8 weeks as compared with the control killed F3 NSC (p,0.001) or PBS groups (p<0.001). These results indicate that the stable immortalized human NSCs are a valuable source of cells for cell replacement and gene transfer for the treatment of ICH and other human neurological disorders.