TY - JOUR
T1 - Therapeutic effect of BDNF-overexpressing human neural stem cells (HB1.F3.BDNF) in a rodent model of middle cerebral artery occlusion
AU - Chang, Da Jeong
AU - Lee, Nayeon
AU - Choi, Chunggab
AU - Jeon, Iksoo
AU - Oh, Seung Hun
AU - Shin, Dong Ah
AU - Hwang, Tae Sun
AU - Lee, Hong J.
AU - Kim, Seung U.
AU - Moon, Hyeyoung
AU - Hong, Kwan Soo
AU - Kang, Kyung Sun
AU - Song, Jihwan
PY - 2013
Y1 - 2013
N2 - Ischemic stroke mainly caused by middle cerebral artery occlusion (MCAo) represents the major type of stroke; however, there are still very limited therapeutic options for the stroke-damaged patients. In this study, we evaluated the neurogenic and therapeutic potentials of human neural stem cells (NSCs) overexpressing brain-derived neurotrophic factor (HB1.F3.BDNF) following transplantation into a rodent model of MCAo. F3.BDNF human NSCs (F3.BDNF) were transplanted into the contralateral side of striatum at 7 days after MCAo, and the transplanted animals were monitored up to 8 weeks using animal MRI and various behavioral tests before they were sacrificed for immunohistochemical analysis. Interestingly, animal MRI results indicate that the majority of contralaterally transplanted neural stem cells were migrated to the peri-infarct area, show ing a pathotropism. Transplanted animals exhibited significant behavioral improvements in stepping, rotarod, and modified neurological severity score (mNSS) tests. We also found that the transplanted human cells were colocalized with nestin, DCX, MAP2, DARPP-32, TH, GAD65/67-positive cells, of which results can be correlated with neural regeneration and behavioral recovery in the transplanted animals. More importantly, we were able to detect high levels of human BDNF protein expression, presumably derived from the transplanted F3.BDNF. Taken together, these results provide strong evidence that human neural stem cells (F3.BDNF) are effective in treating stroke animal models.
AB - Ischemic stroke mainly caused by middle cerebral artery occlusion (MCAo) represents the major type of stroke; however, there are still very limited therapeutic options for the stroke-damaged patients. In this study, we evaluated the neurogenic and therapeutic potentials of human neural stem cells (NSCs) overexpressing brain-derived neurotrophic factor (HB1.F3.BDNF) following transplantation into a rodent model of MCAo. F3.BDNF human NSCs (F3.BDNF) were transplanted into the contralateral side of striatum at 7 days after MCAo, and the transplanted animals were monitored up to 8 weeks using animal MRI and various behavioral tests before they were sacrificed for immunohistochemical analysis. Interestingly, animal MRI results indicate that the majority of contralaterally transplanted neural stem cells were migrated to the peri-infarct area, show ing a pathotropism. Transplanted animals exhibited significant behavioral improvements in stepping, rotarod, and modified neurological severity score (mNSS) tests. We also found that the transplanted human cells were colocalized with nestin, DCX, MAP2, DARPP-32, TH, GAD65/67-positive cells, of which results can be correlated with neural regeneration and behavioral recovery in the transplanted animals. More importantly, we were able to detect high levels of human BDNF protein expression, presumably derived from the transplanted F3.BDNF. Taken together, these results provide strong evidence that human neural stem cells (F3.BDNF) are effective in treating stroke animal models.
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U2 - 10.3727/096368912X657323
DO - 10.3727/096368912X657323
M3 - Article
C2 - 23044072
AN - SCOPUS:84881004658
VL - 22
SP - 1441
EP - 1452
JO - Cell Transplantation
JF - Cell Transplantation
SN - 0963-6897
IS - 8
ER -