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Human neural stem cells genetically modified to overexpress brain‐derived neurotrophic factor promote functional recovery and neuroprotection in a mouse stroke model
Author(s) -
Lee Hong J.,
Lim In J.,
Lee Min C.,
Kim Seung U.
Publication year - 2010
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22474
Subject(s) - neural stem cell , neurotrophic factors , neuroprotection , transplantation , brain derived neurotrophic factor , neuroscience , angiogenesis , medicine , stem cell , pharmacology , biology , microbiology and biotechnology , receptor
Abstract Intracerebral hemorrhage (ICH) is a lethal stroke type; mortality approaches 50%, and current medical therapy against ICH shows only limited effectiveness, so an alternative approach is required, such as stem cell‐based cell therapy. Previously we have shown that intravenously transplanted human neural stem cells (NSCs) selectively migrate to the brain and promote functional recovery in rat ICH model, and others have shown that intracerebral infusion of brain‐derived neurotrophic factor (BDNF) results in improved structural and functional outcome from cerebral ischemia. We postulated that human NSCs overexpressing BDNF transplanted into cerebral cortex overlying ICH lesion could provide improved survival of grafted NSCs and increased angiogenesis and behavioral recovery in mouse ICH model. ICH was induced in adult mice by injection of bacterial collagenase into striatum. The HB1.F3.BDNF (F3.BDNF) human NSC line produces sixfold higher amounts of BDNFF over the parental F3 cell line in vitro, induces behavioral improvement, and produces a threefold increase in cell survival at 2 weeks and 8 weeks posttransplantation. Brain transplantation of human NSCs overexpressing BDNF provided differentiation and survival of grafted human NSCs and renewed angiogenesis of host brain and functional recovery of ICH animals. These results indicate that the F3.BDNF human NSCs should be of great value as a cellular source for experimental studies involving cellular therapy for human neurological disorders, including ICH. © 2010 Wiley‐Liss, Inc.