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into the lesion site could provide long-term improved survival of hNSCs, and
behavioral recovery in mouse ICH model. F3 hNSC was genetically modi-
fied with a mouse Akt1 gene using a retroviral vector. F3 hNSCs expressing
Akt1 were found to be highly resistant to H2O2-induced cytotoxicity in vit-
ro. Following transplantation in ICH mouse brain, F3.Akt1 hNSCs induced
behavioral improvement and significantly increased cell survival (50-100%
increase) at 2 and 8 weeks post-transplantation as compared to parental F3
hNSCs. Brain transplantation of hNSCs overexpressing Akt1 in ICH ani-
mals provided functional recovery, and survival and differentiation of graft-
ed hNSCs. These results indicate that the F3.Akt1 human NSCs should be
a great value as a cellular source for the cellular therapy in animal models of
human neurological disorders including ICH.
introduction
Two major types of stroke are cerebral infarction (ischemia) and intracerebral
hemorrhage (ICH). ICH causes severe neurological deficits and extensive death
rate in patients. Since medical therapy against ICH such as mechanical removal of
hematoma, prevention of edema formation by drugs and reduction of intracranial
pressure shows only limited effectiveness, alternative approach is required such as
stem cell-based cell therapy [1], [2].
Recent progress in stem cell biology has opened up a new way to therapeutic
strategies to replace lost neural cells by transplantation of neural stem cells (NSCs)
in CNS injury and disease [3]-[8]. Previous studies have indicated that NSCs or
neural progenitor cells engrafted in animal models of stroke survive and amelio-
rate neurological deficits in the animals [9]-[17]. Among these studies, human
neural progenitor cells isolated from fetal brain have been transplanted into the
brain of stroke animal models and found to restore brain function [13], [14]. This
approach, however, is not widely acceptable for stroke patients because of moral,
religious and logistic problems associated with the use of human fetal tissues. In
addition, primary human NSCs derived from fetal tissues can be provided for
only a limited time before they undergo senescence, and it is difficult to secure
sufficient numbers and homogeneous populations of human NSCs from fetal
brain. These problems can be circumvented by the use of stable, permanent cell
lines of human NSCs. We have previously reported that human NSC line amelio-
rate neurological deficits in animal models of Parkinson disease [18], Huntington
disease [19], [20], amyotrophic lateral sclerosis [21] and lysosomal storage disease
[22] following their transplantation into the brain or spinal cord. In stroke ani-
mal models, intravenously transplanted human NSCs migrated selectively to the
damaged brain sites caused by ischemia and ICH, differentiated into neurons and
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