TY - JOUR
T1 - Transplantation of primed human fetal neural stem cells improves cognitive function in rats after traumatic brain injury
AU - Gao, Junling
AU - Prough, Donald S.
AU - McAdoo, David J.
AU - Grady, James J.
AU - Parsley, Margaret O.
AU - Ma, Long
AU - Tarensenko, Yevgeniya I.
AU - Wu, Ping
N1 - Funding Information:
The authors would like to thank Tiffany Dunn and Michael Hughes for technical support, Paivi Jordan and Patricia Gazzoli for manuscript preparation and Richard Coggeshall for critical review. This work was supported by the Coalition for Brain Injury Research (pw), the TIRR Foundation (pw), NIH (NS046025) (pw) and NIH (NS042849) (dp).
PY - 2006/10
Y1 - 2006/10
N2 - Traumatic brain injury (TBI) often produces cognitive impairments by primary or secondary neuronal loss. Stem cells are a potential tool to treat TBI. However, most previous studies using rodent stem or progenitor cells failed to correlate cell grafting and cognitive improvement. Furthermore, the efficacy of fetal human neural stem cells (hNSCs) for ameliorating TBI cognitive dysfunction is undetermined. This study therefore characterized phenotypic differentiation, neurotrophic factor expression and release and functional outcome of grafting hNSCs into TBI rat brains. Adult Sprague-Dawley rats underwent a moderate parasagittal fluid percussion TBI followed by ipsilateral hippocampal transplantation of hNSCs or vehicle 1 day post-injury. Prior to grafting, hNSCs were treated in vitro for 7 days with our previously developed priming procedure. Significant spatial learning and memory improvements were detected by the Morris water maze (MWM) test in rats 10 days after receiving hNSC grafts. Morphological analyses revealed that hNSCs survived and differentiated mainly into neurons in the injured hippocampus at 2 weeks after grafting. Furthermore, hNSCs expressed and released glial-cell-line-derived neurotrophic factor (GDNF) in vitro and when grafted in vivo, as detected by RT-PCR, immunostaining, microdialysis and ELISA. This is the first direct demonstration of the release of a neurotrophic factor in conjunction with stem cell grafting. In conclusion, human fetal neural stem cell grafts improved cognitive function of rats with acute TBI. Grafted cells survived and differentiated into neurons and expressed and released GNDF in vivo, which may help protect host cells from secondary damage and aid host regeneration.
AB - Traumatic brain injury (TBI) often produces cognitive impairments by primary or secondary neuronal loss. Stem cells are a potential tool to treat TBI. However, most previous studies using rodent stem or progenitor cells failed to correlate cell grafting and cognitive improvement. Furthermore, the efficacy of fetal human neural stem cells (hNSCs) for ameliorating TBI cognitive dysfunction is undetermined. This study therefore characterized phenotypic differentiation, neurotrophic factor expression and release and functional outcome of grafting hNSCs into TBI rat brains. Adult Sprague-Dawley rats underwent a moderate parasagittal fluid percussion TBI followed by ipsilateral hippocampal transplantation of hNSCs or vehicle 1 day post-injury. Prior to grafting, hNSCs were treated in vitro for 7 days with our previously developed priming procedure. Significant spatial learning and memory improvements were detected by the Morris water maze (MWM) test in rats 10 days after receiving hNSC grafts. Morphological analyses revealed that hNSCs survived and differentiated mainly into neurons in the injured hippocampus at 2 weeks after grafting. Furthermore, hNSCs expressed and released glial-cell-line-derived neurotrophic factor (GDNF) in vitro and when grafted in vivo, as detected by RT-PCR, immunostaining, microdialysis and ELISA. This is the first direct demonstration of the release of a neurotrophic factor in conjunction with stem cell grafting. In conclusion, human fetal neural stem cell grafts improved cognitive function of rats with acute TBI. Grafted cells survived and differentiated into neurons and expressed and released GNDF in vivo, which may help protect host cells from secondary damage and aid host regeneration.
KW - Cognitive function
KW - Glial-cell-line-derived neurotrophic factor
KW - Hippocampus
KW - Neural stem cell
KW - Transplantation
KW - Traumatic brain injury
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U2 - 10.1016/j.expneurol.2006.04.039
DO - 10.1016/j.expneurol.2006.04.039
M3 - Article
C2 - 16904107
AN - SCOPUS:33748423523
SN - 0014-4886
VL - 201
SP - 281
EP - 292
JO - Experimental Neurology
JF - Experimental Neurology
IS - 2
ER -