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TISSUE-SPECIFIC STEM CELLS

Brain Transplantation of Immortalized Human Neural Stem Cells Promotes Functional Recovery in Mouse Intracerebral Hemorrhage Stroke Model

^aBrain Disease Research Center, Ajou University School of Medicine, Suwon, Korea;
^bDepartment of Animal Science, Korea University, Seoul, Korea;
^cDivision of Neurology, Department of Medicine, University of British Columbia Hospital, University of British Columbia, Vancouver, Canada;
^dNational Veterinary Research and Quarantine Services, Anyang, Korea;
^eDepartment of Neurology, Ilsan Paik Hospital, Goyang, Korea

Key Words. Human neural stem cell • Permanent cell line • Intracerebral hemorrhage • Stroke • Brain transplantation • Cell therapy

Correspondence: Seung U. Kim, M.D., Ph.D., Division of Neurology, Department of Medicine, University of British Columbia Hospital, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada. Telephone: 604-822-7145; Fax: 604-822-7897; e-mail: sukim{at}interchange.ubc.ca

Received July 6, 2006; accepted for publication December 28, 2006.
First published online in STEM CELLS EXPRESS   January 11, 2007.



We have generated stable, immortalized cell lines of human NSCs from primary human fetal telencephalon cultures via a retroviral vector encoding v-myc. HB1.F3, one of the human NSC lines, expresses a normal human karyotype of 46, XX, and nestin, a cell type-specific marker for NSCs. F3 has the ability to proliferate continuously and differentiate into cells of neuronal and glial lineage. The HB1.F3 human NSC line was used for cell therapy in a mouse model of intracerebral hemorrhage (ICH) stroke. Experimental ICH was induced in adult mice by intrastriatal administration of bacterial collagenase; 1 week after surgery, the rats were randomly divided into two groups so as to receive intracerebrally either human NSCs labeled with β-galactosidase (n = 31) or phosphate-buffered saline (PBS) (n = 30). Transplanted NSCs were detected by 5-bromo-4-chloro-3-indolyl-β-D-galactoside histochemistry or double labeling with β-galactosidase (β-gal) and mitogen-activated protein (MAP)2, neurofilaments (both for neurons), or glial fibrillary acidic protein (GFAP) (for astrocytes). Behavior of the animals was evaluated for period up to 8 weeks using modified Rotarod tests and a limb placing test. Transplanted human NSCs were identified in the perihematomal areas and differentiated into neurons (β-gal/MAP2⁺ and β-gal/NF⁺) or astrocytes (β-gal/GFAP⁺). The NSC-transplanted group showed markedly improved functional performance on the Rotarod test and limb placing after 2–8 weeks compared with the control PBS group (p < .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.

Disclosure of potential conflicts of interest is found at the end of this article.