TY - CHAP
T1 - NT2N Cell Transplantation and GDNF Treatment in Stroke
T2 - Linking Neurotrophic Factor Therapy and Neuroprotection
AU - Borlongan, Cesario V.
AU - Stahl, Christine E.
AU - Yu, Guolong
AU - Xu, Lin
AU - Yasuhara, Takao
AU - Hara, Koichi
AU - Matsukawa, Noriyuki
AU - Sanberg, Paul R.
AU - Wang, Yun
AU - Hess, David C.
N1 - Funding Information:
CVB is supported by the VA VISN7 Career Development Award, the VA Merit Review, and the American Heart Association Grant-in-Aid Award.
PY - 2007
Y1 - 2007
N2 - Accumulating scientific evidence demonstrates that diseased or aging brain cells can potentially be rescued and have their functions restored. Cell replacement therapy has emerged as the current translational research trend and in the future could provide a promising treatment intervention for various neurological disorders. One of the many nonfetal cell lines is the embryonal carcinoma cell line (NT2 cells) that are transfectable and capable of differentiating into postmitotic neuron-like cells (NT2N cells) following treatment with retinoic acid, thereby allowing this human neuronal cell line to serve as a platform for gene therapy applications for treating CNS disorders. The phenotypic characteristics of both NT2 and NT2N cells suggest the likelihood that they are an excellent platform for ex vivo gene therapy in the CNS. Additionally, exogenous treatment with glial-cell-line-derived neurotrophic factor (GDNF) has provided symptomatic relief in animal models of neurological disorders. Two neurological disorders that have been the target of GDNF therapy include stroke and Parkinson's disease (PD). Both stroke and PD lead to long-term and debilitating abnormalities in victims. Initial evidence of GDNF neuroprotective and regenerative effects was described in midbrain dopamine neurons, but subsequently extended to other CNS regions. Because of overlapping etiologies between stroke and PD, therapeutic outcomes with GDNF in either one or both diseases have contributed to the increased interest in our understanding of neuronal cell death-as well as to the development of neurotrophic-factor-based treatment strategies.
AB - Accumulating scientific evidence demonstrates that diseased or aging brain cells can potentially be rescued and have their functions restored. Cell replacement therapy has emerged as the current translational research trend and in the future could provide a promising treatment intervention for various neurological disorders. One of the many nonfetal cell lines is the embryonal carcinoma cell line (NT2 cells) that are transfectable and capable of differentiating into postmitotic neuron-like cells (NT2N cells) following treatment with retinoic acid, thereby allowing this human neuronal cell line to serve as a platform for gene therapy applications for treating CNS disorders. The phenotypic characteristics of both NT2 and NT2N cells suggest the likelihood that they are an excellent platform for ex vivo gene therapy in the CNS. Additionally, exogenous treatment with glial-cell-line-derived neurotrophic factor (GDNF) has provided symptomatic relief in animal models of neurological disorders. Two neurological disorders that have been the target of GDNF therapy include stroke and Parkinson's disease (PD). Both stroke and PD lead to long-term and debilitating abnormalities in victims. Initial evidence of GDNF neuroprotective and regenerative effects was described in midbrain dopamine neurons, but subsequently extended to other CNS regions. Because of overlapping etiologies between stroke and PD, therapeutic outcomes with GDNF in either one or both diseases have contributed to the increased interest in our understanding of neuronal cell death-as well as to the development of neurotrophic-factor-based treatment strategies.
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U2 - 10.1016/B978-012369415-7/50021-1
DO - 10.1016/B978-012369415-7/50021-1
M3 - Chapter
AN - SCOPUS:79955381370
SN - 9780123694157
SP - 353
EP - 371
BT - Cellular Transplantation
PB - Elsevier Inc.
ER -