Combined treatment of vascular endothelial growth factor and human neural stem cells in experimental focal cerebral ischemia

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Chu, Kon; Park, Kyung-Il; Lee, Soon-Tae; Jung, Keun-Hwa; Ko, Song-Yi; Kang, Lami; Sinn, Dong-In; Lee, Yong-Seok; Kim, Seung U; Kim, Manho; Roh, Jae-Kyu
Issue Date
Neurosci Res. 2005 Dec;53(4):384-90. Epub 2005 Sep 28.
AnimalsBrain/blood supply/pathologyBrain Ischemia/pathology/*therapyCell LineCell TransplantationHumansMaleNeurons/*transplantationRatsRats, Sprague-DawleyRecovery of Function*Stem Cell TransplantationVascular Endothelial Growth Factor A/*therapeutic use
Recent studies have indicated the beneficial effects of vascular endothelial growth factor (VEGF), and transplanted neural stem cells (NSCs) in cerebral ischemia. We investigated the effects of the combined administration of NSCs and VEGF on focal cerebral ischemia in adult rats. Four groups (n = 12, respectively)--group 1 (ischemia-only), group 2 (ischemia + VEGF), group 3 (ischemia + NSCs) and group 4 (ischemia + NSCs + VEGF)--were compared. Human NSCs (HB1.F3), labeled with Lac Z+ or PKH26, were given intravenously 24h after surgery (5 x 10(6) cells). At 48 h after surgery, recombinant human VEGF (50 microg/kg) was infused intravenously (1 microg/(kg min)). Behavioral tests using the modified limb placing and rotarod tests were performed every week following ischemia. Immunohistochemistry for endothelial barrier antigen (EBA), VEGF and Nissl staining were performed at day 35 after ischemia. Group 4 showed better behavioral recovery at 7, 14 and 28 days than group 3 (p = 0.020, 0.005 and 0.043, respectively). These functional recoveries were correlated with enhanced EBA immunoreactivities at day 35 after ischemia, especially in the ipsilesional striatum. Group 4 showed lesser degree of brain atrophy in cortex and striatum, when compared with other groups. The distribution of VEGF was not co-localized with NSCs. Our results suggest that VEGF may act synergistically on NSC-transplanted, ischemic brain via a pro-angiogenic effect.
0168-0102 (Print)
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Neurology (신경과학교실)Journal Papers (저널논문_신경과학교실)
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