Human neural stem cell transplantation promotes functional recovery in rats with experimental intracerebral hemorrhage.

Abstract

BACKGROUND AND PURPOSE: Cell transplantation has been used to reduce behavioral deficit in cerebral ischemia. However, there is no report about cell transplantation in experimental intracerebral hemorrhage (ICH). We hypothesize that intravenously transplanted human neural stem cells (NSCs) can migrate and differentiate into neurons or glial cells, thereby improving functional outcome in ICH.

METHODS: Experimental ICH was induced by intrastriatal administration of bacterial collagenase in adult rats. One day after surgery, the rats were randomly divided into 2 groups to receive intravenously either immortalized Lac z-positive human NSCs (5x10(6) cells in 500 microL, n=12) or the same amount of saline (n=13). The animals were evaluated for 8 weeks with modified limb placing and rotarod tests. Transplanted NSCs were detected by X-gal histochemistry or beta-gal immunohistochemistry with double labeling of GFAP, NeuN, neurofilament, or CNPase.

RESULTS: Intravenously transplanted NSCs migrated selectively to the perihematomal areas and differentiated into neurons (approximately 10% of beta-gal+ cells) and astrocytes (approximately 75%). The NSC-transplanted group showed better functional performance on rotarod test after 2 weeks and on modified limb placing test after 5 weeks compared with the control group (P<0.05), and these effects persisted for up to 8 weeks. There was no difference in the final hemispheric area between the 2 groups.

CONCLUSIONS: Intravenously transplanted NSCs can enter the rat brain with ICH, survive, migrate, and improve functional recovery. Transplantation of human NSCs can be used to restore neurological deficits in experimental ICH.