Combined treatment of vascular endothelial growth factor and human neural stem cells in experimental focal cerebral ischemia.
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.
Chu
Kon
K
Stroke & Neural Stem Cell Laboratory in Clinical Research Institute, Department of Neurology, Seoul National University Hospital, 28, Yongon-dong, Chongro-gu, Seoul 110-744, South Korea.
Park
Kyung-Il
KI
Lee
Soon-Tae
ST
Jung
Keun-Hwa
KH
Ko
Song-Yi
SY
Kang
Lami
L
Sinn
Dong-In
DI
Lee
Yong-Seok
YS
Kim
Seung U
SU
Kim
Manho
M
Roh
Jae-Kyu
JK
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology / Q000628:therapy*; D002460:Cell Line; D017690:Cell Transplantation; D006801:Humans; D008297:Male; D009474:Neurons / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D033581:Stem Cell Transplantation; D042461:Vascular Endothelial Growth Factor A / Q000627:therapeutic use*
D042461:Vascular Endothelial Growth Factor A