The Experts below are selected from a list of 19278 Experts worldwide ranked by ideXlab platform
Hong J. Lee - One of the best experts on this subject based on the ideXlab platform.
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Multilineage Potential of Stable Human Mesenchymal Stem Cell Line Derived from Fetal Marrow
2013Co-Authors: Atsushi Nagai, Woo K. Kim, Hong J. Lee, Han S. Jeong, Kwang S. Kim, Seok H. Hong, In H. Park, Seung U. KimAbstract:Human bone marrow contains two major cell types, hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). MSCs possess self-renewal capacity and pluripotency defined by their ability to differentiate into osteoblasts, chondrocytes, adipocytes and muscle cells. MSCs are also known to differentiate into neurons and glial cells in vitro, and in vivo following Transplantation into the Brain of animal models of neurological disorders including ischemia and intracerebral hemorrhage (ICH) stroke. In order to obtain sufficient number and homogeneous population of human MSCs, we have clonally isolated permanent and stable human MSC lines by transfecting primary cell cultures of fetal human bone marrow MSCs with a retroviral vector encoding v-myc gene. One of the cell lines, HM3.B10 (B10), was found to differentiate into neural cell types including neural stem cells, neurons, astrocytes and oligodendrocytes in vitro as shown by expression of genetic markers for neural stem cells (nestin and Musashi1), neurons (neurofilament protein, synapsin and MAP2), astrocytes (glial fibrillary acidic protein, GFAP) and oligodendrocytes (myelin basic protein, MBP) as determined by RT-PCR assay. In addition, B10 cells were found to differentiate into neural cell types as shown by immunocytochical demonstration of nestin (for neural stem cells), neurofilament protein and b-tubulin III (neurons) GFAP (astrocytes), and galactocerebroside (oligodendrocytes). Following Brain Transplantation in mouse ICH stroke model, B10 human MSCs integrate into host Brain, survive, differentiate into neurons and astrocytes and induce behavioral improvement in the ICH animals. B10 human MSC cell line is not only a useful tool for the studies of organogenesis and specifically for the neurogenesis, but also provides a valuable source of cells for cel
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human neural stem cells genetically modified to overexpress Brain derived neurotrophic factor promote functional recovery and neuroprotection in a mouse stroke model
Journal of Neuroscience Research, 2010Co-Authors: Hong J. Lee, Seung U. Kim, In J Lim, Min C LeeAbstract:Intracerebral hemorrhage (ICH) is a lethal stroke type; mortality approaches 50%, and current medical therapy against ICH shows only limited effectiveness, so an alternative approach is required, such as stem cell-based cell therapy. Previously we have shown that intravenously transplanted human neural stem cells (NSCs) selectively migrate to the Brain and promote functional recovery in rat ICH model, and others have shown that intracerebral infusion of Brain-derived neurotrophic factor (BDNF) results in improved structural and functional outcome from cerebral ischemia. We postulated that human NSCs overexpressing BDNF transplanted into cerebral cortex overlying ICH lesion could provide improved survival of grafted NSCs and increased angiogenesis and behavioral recovery in mouse ICH model. ICH was induced in adult mice by injection of bacterial collagenase into striatum. The HB1.F3.BDNF (F3.BDNF) human NSC line produces sixfold higher amounts of BDNFF over the parental F3 cell line in vitro, induces behavioral improvement, and produces a threefold increase in cell survival at 2 weeks and 8 weeks postTransplantation. Brain Transplantation of human NSCs overexpressing BDNF provided differentiation and survival of grafted human NSCs and renewed angiogenesis of host Brain and functional recovery of ICH animals. These results indicate that the F3.BDNF human NSCs should be of great value as a cellular source for experimental studies involving cellular therapy for human neurological disorders, including ICH.
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multilineage potential of stable human mesenchymal stem cell line derived from fetal marrow
PLOS ONE, 2007Co-Authors: Atsushi Nagai, Woo K. Kim, Hong J. Lee, Han S. Jeong, Kwang S. Kim, Seok H. Hong, In H. ParkAbstract:Human bone marrow contains two major cell types, hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). MSCs possess self-renewal capacity and pluripotency defined by their ability to differentiate into osteoblasts, chondrocytes, adipocytes and muscle cells. MSCs are also known to differentiate into neurons and glial cells in vitro, and in vivo following Transplantation into the Brain of animal models of neurological disorders including ischemia and intracerebral hemorrhage (ICH) stroke. In order to obtain sufficient number and homogeneous population of human MSCs, we have clonally isolated permanent and stable human MSC lines by transfecting primary cell cultures of fetal human bone marrow MSCs with a retroviral vector encoding v-myc gene. One of the cell lines, HM3.B10 (B10), was found to differentiate into neural cell types including neural stem cells, neurons, astrocytes and oligodendrocytes in vitro as shown by expression of genetic markers for neural stem cells (nestin and Musashi1), neurons (neurofilament protein, synapsin and MAP2), astrocytes (glial fibrillary acidic protein, GFAP) and oligodendrocytes (myelin basic protein, MBP) as determined by RT-PCR assay. In addition, B10 cells were found to differentiate into neural cell types as shown by immunocytochical demonstration of nestin (for neural stem cells), neurofilament protein and β-tubulin III (neurons) GFAP (astrocytes), and galactocerebroside (oligodendrocytes). Following Brain Transplantation in mouse ICH stroke model, B10 human MSCs integrate into host Brain, survive, differentiate into neurons and astrocytes and induce behavioral improvement in the ICH animals. B10 human MSC cell line is not only a useful tool for the studies of organogenesis and specifically for the neurogenesis, but also provides a valuable source of cells for cell therapy studies in animal models of stroke and other neurological disorders.
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Brain Transplantation of immortalized human neural stem cells promotes functional recovery in mouse intracerebral hemorrhage stroke model
Stem Cells, 2007Co-Authors: Hong J. Lee, Hyun B Choi, Kwang Soo Kim, Eun Ju Kim, Kwang Hoon Lee, In H. ParkAbstract:We have generated stable, immortalized cell lines of human NSCs from primary human fetal telencephalon cultures via a retroviral vector encoding v-myc. HB1.F3, one of the human NSC lines, expresses a normal human karyotype of 46, XX, and nestin, a cell type-specific marker for NSCs. F3 has the ability to proliferate continuously and differentiate into cells of neuronal and glial lineage. The HB1.F3 human NSC line was used for cell therapy in a mouse model of intracerebral hemorrhage (ICH) stroke. Experimental ICH was induced in adult mice by intrastriatal administration of bacterial collagenase; 1 week after surgery, the rats were randomly divided into two groups so as to receive intracerebrally either human NSCs labeled with beta-galactosidase (n = 31) or phosphate-buffered saline (PBS) (n = 30). Transplanted NSCs were detected by 5-bromo-4-chloro-3-indolyl-beta-d-galactoside histochemistry or double labeling with beta-galactosidase (beta-gal) and mitogen-activated protein (MAP)2, neurofilaments (both for neurons), or glial fibrillary acidic protein (GFAP) (for astrocytes). Behavior of the animals was evaluated for period up to 8 weeks using modified Rotarod tests and a limb placing test. Transplanted human NSCs were identified in the perihematomal areas and differentiated into neurons (beta-gal/MAP2(+) and beta-gal/NF(+)) or astrocytes (beta-gal/GFAP(+)). The NSC-transplanted group showed markedly improved functional performance on the Rotarod test and limb placing after 2-8 weeks compared with the control PBS group (p < .001). These results indicate that the stable immortalized human NSCs are a valuable source of cells for cell replacement and gene transfer for the treatment of ICH and other human neurological disorders. Disclosure of potential conflicts of interest is found at the end of this article.
In H. Park - One of the best experts on this subject based on the ideXlab platform.
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Multilineage Potential of Stable Human Mesenchymal Stem Cell Line Derived from Fetal Marrow
2013Co-Authors: Atsushi Nagai, Woo K. Kim, Hong J. Lee, Han S. Jeong, Kwang S. Kim, Seok H. Hong, In H. Park, Seung U. KimAbstract:Human bone marrow contains two major cell types, hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). MSCs possess self-renewal capacity and pluripotency defined by their ability to differentiate into osteoblasts, chondrocytes, adipocytes and muscle cells. MSCs are also known to differentiate into neurons and glial cells in vitro, and in vivo following Transplantation into the Brain of animal models of neurological disorders including ischemia and intracerebral hemorrhage (ICH) stroke. In order to obtain sufficient number and homogeneous population of human MSCs, we have clonally isolated permanent and stable human MSC lines by transfecting primary cell cultures of fetal human bone marrow MSCs with a retroviral vector encoding v-myc gene. One of the cell lines, HM3.B10 (B10), was found to differentiate into neural cell types including neural stem cells, neurons, astrocytes and oligodendrocytes in vitro as shown by expression of genetic markers for neural stem cells (nestin and Musashi1), neurons (neurofilament protein, synapsin and MAP2), astrocytes (glial fibrillary acidic protein, GFAP) and oligodendrocytes (myelin basic protein, MBP) as determined by RT-PCR assay. In addition, B10 cells were found to differentiate into neural cell types as shown by immunocytochical demonstration of nestin (for neural stem cells), neurofilament protein and b-tubulin III (neurons) GFAP (astrocytes), and galactocerebroside (oligodendrocytes). Following Brain Transplantation in mouse ICH stroke model, B10 human MSCs integrate into host Brain, survive, differentiate into neurons and astrocytes and induce behavioral improvement in the ICH animals. B10 human MSC cell line is not only a useful tool for the studies of organogenesis and specifically for the neurogenesis, but also provides a valuable source of cells for cel
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multilineage potential of stable human mesenchymal stem cell line derived from fetal marrow
PLOS ONE, 2007Co-Authors: Atsushi Nagai, Woo K. Kim, Hong J. Lee, Han S. Jeong, Kwang S. Kim, Seok H. Hong, In H. ParkAbstract:Human bone marrow contains two major cell types, hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). MSCs possess self-renewal capacity and pluripotency defined by their ability to differentiate into osteoblasts, chondrocytes, adipocytes and muscle cells. MSCs are also known to differentiate into neurons and glial cells in vitro, and in vivo following Transplantation into the Brain of animal models of neurological disorders including ischemia and intracerebral hemorrhage (ICH) stroke. In order to obtain sufficient number and homogeneous population of human MSCs, we have clonally isolated permanent and stable human MSC lines by transfecting primary cell cultures of fetal human bone marrow MSCs with a retroviral vector encoding v-myc gene. One of the cell lines, HM3.B10 (B10), was found to differentiate into neural cell types including neural stem cells, neurons, astrocytes and oligodendrocytes in vitro as shown by expression of genetic markers for neural stem cells (nestin and Musashi1), neurons (neurofilament protein, synapsin and MAP2), astrocytes (glial fibrillary acidic protein, GFAP) and oligodendrocytes (myelin basic protein, MBP) as determined by RT-PCR assay. In addition, B10 cells were found to differentiate into neural cell types as shown by immunocytochical demonstration of nestin (for neural stem cells), neurofilament protein and β-tubulin III (neurons) GFAP (astrocytes), and galactocerebroside (oligodendrocytes). Following Brain Transplantation in mouse ICH stroke model, B10 human MSCs integrate into host Brain, survive, differentiate into neurons and astrocytes and induce behavioral improvement in the ICH animals. B10 human MSC cell line is not only a useful tool for the studies of organogenesis and specifically for the neurogenesis, but also provides a valuable source of cells for cell therapy studies in animal models of stroke and other neurological disorders.
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Brain Transplantation of immortalized human neural stem cells promotes functional recovery in mouse intracerebral hemorrhage stroke model
Stem Cells, 2007Co-Authors: Hyun B Choi, In H. Park, Yong Ko, Sang W JeongAbstract:We have generated stable, immortalized cell lines of human NSCs from primary human fetal telencephalon cultures via a retroviral vector encoding v-myc. HB1.F3, one of the human NSC lines, expresses a normal human karyotype of 46, XX, and nestin, a cell type-specific marker for NSCs. F3 has the ability to proliferate continuously and differentiate into cells of neuronal and glial lineage. The HB1.F3 human NSC line was used for cell therapy in a mouse model of intracerebral hemorrhage (ICH) stroke. Experimental ICH was induced in adult mice by intrastriatal administration of bacterial collagenase; 1 week after surgery, the rats were randomly divided into two groups so as to receive intracerebrally either human NSCs labeled with -galactosidase (n 31) or phosphate-buffered saline (PBS) (n 30). Transplanted NSCs were detected by 5-bromo-4-chloro-3indolyl--D-galactoside histochemistry or double labeling with -galactosidase (-gal) and mitogen-activated protein (MAP)2, neurofilaments (both for neurons), or glial fibrillary acidic protein (GFAP) (for astrocytes). Behavior of the animals was evaluated for period up to 8 weeks using modified Rotarod tests and a limb placing test. Transplanted human NSCs were identified in the perihematomal areas and differentiated into neurons (-gal/MAP2 and -gal/ NF) or astrocytes (-gal/GFAP). The NSC-transplanted group showed markedly improved functional performance on the Rotarod test and limb placing after 2–8 weeks compared with the control PBS group (p < .001). These results indicate that the stable immortalized human NSCs are a valuable source of cells for cell replacement and gene transfer for the treatment of ICH and other human neurological disorders. STEM CELLS 2007;25: 1204–1212
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Brain Transplantation of immortalized human neural stem cells promotes functional recovery in mouse intracerebral hemorrhage stroke model
Stem Cells, 2007Co-Authors: Hong J. Lee, Hyun B Choi, Kwang Soo Kim, Eun Ju Kim, Kwang Hoon Lee, In H. ParkAbstract:We have generated stable, immortalized cell lines of human NSCs from primary human fetal telencephalon cultures via a retroviral vector encoding v-myc. HB1.F3, one of the human NSC lines, expresses a normal human karyotype of 46, XX, and nestin, a cell type-specific marker for NSCs. F3 has the ability to proliferate continuously and differentiate into cells of neuronal and glial lineage. The HB1.F3 human NSC line was used for cell therapy in a mouse model of intracerebral hemorrhage (ICH) stroke. Experimental ICH was induced in adult mice by intrastriatal administration of bacterial collagenase; 1 week after surgery, the rats were randomly divided into two groups so as to receive intracerebrally either human NSCs labeled with beta-galactosidase (n = 31) or phosphate-buffered saline (PBS) (n = 30). Transplanted NSCs were detected by 5-bromo-4-chloro-3-indolyl-beta-d-galactoside histochemistry or double labeling with beta-galactosidase (beta-gal) and mitogen-activated protein (MAP)2, neurofilaments (both for neurons), or glial fibrillary acidic protein (GFAP) (for astrocytes). Behavior of the animals was evaluated for period up to 8 weeks using modified Rotarod tests and a limb placing test. Transplanted human NSCs were identified in the perihematomal areas and differentiated into neurons (beta-gal/MAP2(+) and beta-gal/NF(+)) or astrocytes (beta-gal/GFAP(+)). The NSC-transplanted group showed markedly improved functional performance on the Rotarod test and limb placing after 2-8 weeks compared with the control PBS group (p < .001). These results indicate that the stable immortalized human NSCs are a valuable source of cells for cell replacement and gene transfer for the treatment of ICH and other human neurological disorders. Disclosure of potential conflicts of interest is found at the end of this article.
Seung U. Kim - One of the best experts on this subject based on the ideXlab platform.
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Multilineage Potential of Stable Human Mesenchymal Stem Cell Line Derived from Fetal Marrow
2013Co-Authors: Atsushi Nagai, Woo K. Kim, Hong J. Lee, Han S. Jeong, Kwang S. Kim, Seok H. Hong, In H. Park, Seung U. KimAbstract:Human bone marrow contains two major cell types, hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). MSCs possess self-renewal capacity and pluripotency defined by their ability to differentiate into osteoblasts, chondrocytes, adipocytes and muscle cells. MSCs are also known to differentiate into neurons and glial cells in vitro, and in vivo following Transplantation into the Brain of animal models of neurological disorders including ischemia and intracerebral hemorrhage (ICH) stroke. In order to obtain sufficient number and homogeneous population of human MSCs, we have clonally isolated permanent and stable human MSC lines by transfecting primary cell cultures of fetal human bone marrow MSCs with a retroviral vector encoding v-myc gene. One of the cell lines, HM3.B10 (B10), was found to differentiate into neural cell types including neural stem cells, neurons, astrocytes and oligodendrocytes in vitro as shown by expression of genetic markers for neural stem cells (nestin and Musashi1), neurons (neurofilament protein, synapsin and MAP2), astrocytes (glial fibrillary acidic protein, GFAP) and oligodendrocytes (myelin basic protein, MBP) as determined by RT-PCR assay. In addition, B10 cells were found to differentiate into neural cell types as shown by immunocytochical demonstration of nestin (for neural stem cells), neurofilament protein and b-tubulin III (neurons) GFAP (astrocytes), and galactocerebroside (oligodendrocytes). Following Brain Transplantation in mouse ICH stroke model, B10 human MSCs integrate into host Brain, survive, differentiate into neurons and astrocytes and induce behavioral improvement in the ICH animals. B10 human MSC cell line is not only a useful tool for the studies of organogenesis and specifically for the neurogenesis, but also provides a valuable source of cells for cel
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human neural stem cells genetically modified to overexpress Brain derived neurotrophic factor promote functional recovery and neuroprotection in a mouse stroke model
Journal of Neuroscience Research, 2010Co-Authors: Hong J. Lee, Seung U. Kim, In J Lim, Min C LeeAbstract:Intracerebral hemorrhage (ICH) is a lethal stroke type; mortality approaches 50%, and current medical therapy against ICH shows only limited effectiveness, so an alternative approach is required, such as stem cell-based cell therapy. Previously we have shown that intravenously transplanted human neural stem cells (NSCs) selectively migrate to the Brain and promote functional recovery in rat ICH model, and others have shown that intracerebral infusion of Brain-derived neurotrophic factor (BDNF) results in improved structural and functional outcome from cerebral ischemia. We postulated that human NSCs overexpressing BDNF transplanted into cerebral cortex overlying ICH lesion could provide improved survival of grafted NSCs and increased angiogenesis and behavioral recovery in mouse ICH model. ICH was induced in adult mice by injection of bacterial collagenase into striatum. The HB1.F3.BDNF (F3.BDNF) human NSC line produces sixfold higher amounts of BDNFF over the parental F3 cell line in vitro, induces behavioral improvement, and produces a threefold increase in cell survival at 2 weeks and 8 weeks postTransplantation. Brain Transplantation of human NSCs overexpressing BDNF provided differentiation and survival of grafted human NSCs and renewed angiogenesis of host Brain and functional recovery of ICH animals. These results indicate that the F3.BDNF human NSCs should be of great value as a cellular source for experimental studies involving cellular therapy for human neurological disorders, including ICH.
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Brain Transplantation of genetically engineered human neural stem cells globally corrects Brain lesions in the mucopolysaccharidosis type vii mouse
Journal of Neuroscience Research, 2003Co-Authors: Xingli Meng, Seung U. Kim, Jinsong Shen, Toya Ohashi, Hiroshi Maeda, Yoshikatsu EtoAbstract:In the present study, we investigated the feasibility of using human neural stem cells (NSCs) in the treatment of diffuse central nervous system (CNS) alterations in a murine model of mucopolysaccharidosis VII (MPS VII), a lysosomal storage disease caused by a genetic defect in the β-glucuronidase gene. An immortalized NSC line derived from human fetal telencephalon was genetically engineered to overexpress β-glucuronidase and transplanted into the cerebral ventricles of neonatal MPS VII mouse. Transplanted human NSCs were found to integrate and migrate in the host Brain and to produce large amount of β-glucuronidase. Brain contents of the substrates of β-glucuronidase were reduced to nearly normal levels, and widespread clearing of lysosomal storage was observed in the MPS VII mouse Brain at 25 days postTransplantation. The number of engrafted cells decreased markedly after the Transplantation, and it appears that the major cause of the cell death was not the immune response of the host but apoptotic cell death of grafted human NSCs. Results showed that human NSCs would serve as a useful gene transfer vehicle for the treatment of diffuse CNS lesions in human lysosomal storage diseases and are potentially applicable in the treatment of patients suffering from neurological disorders. © 2003 Wiley-Liss, Inc.
Ikuo Tooyama - One of the best experts on this subject based on the ideXlab platform.
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human neural stem cells over expressing choline acetyltransferase restore cognition in rat model of cognitive dysfunction
Experimental Neurology, 2012Co-Authors: Dongsun Park, Seong Soo Joo, Hong Jun Lee, Inja Lim, Akinori Matsuo, Daekwon Bae, Goeun Yang, Yunhui Yang, Ikuo TooyamaAbstract:A human neural stem cell (NSC) line over-expressing human choline acetyltransferase (ChAT) gene was generated and these F3.ChAT NSCs were transplanted into the Brain of rat Alzheimer disease (AD) model which was induced by application of ethylcholine mustard aziridinium ion (AF64A) that specifically denatures cholinergic nerves and thereby leads to memory deficit as a salient feature of AD. Transplantation of F3.ChAT human NSCs fully recovered the learning and memory function of AF64A animals, and induced elevated levels of acetylcholine (ACh) in cerebrospinal fluid (CSF). Transplanted F3.ChAT human NSCs were found to migrate to various Brain regions including cerebral cortex, hippocampus, striatum and septum, and differentiated into neurons and astrocytes. The present study demonstrates that Brain Transplantation of human NSCs over-expressing ChAT ameliorates complex learning and memory deficits in AF64A-cholinotoxin-induced AD rat model.
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human neural stem cells overexpressing choline acetyltransferase restore cognitive function of kainic acid induced learning and memory deficit animals
Cell Transplantation, 2012Co-Authors: Dongsun Park, Seong Soo Joo, Tae Kyun Kim, Sun Hee Lee, Hyomin Kang, Hong Jun Lee, Inja Lim, Akinori Matsuo, Ikuo TooyamaAbstract:Alzheimer disease (AD) is a progressive neurodegenerative disease, which is characterized by loss of memory and cognitive function. In AD patients dysfunction of the cholinergic system is the main cause of cognitive disorders, and decreased activity of choline acetyltransferase (ChAT), an enzyme responsible for acetylcholine (ACh) synthesis, is observed. In the present study we investigated if Brain Transplantation of human neural stem cells (NSCs) genetically modified to encode ChAT gene improves cognitive function of kainic acid (KA)-induced learning deficit rats. Intrahippocampal injection of KA to hippocampal CA3 region caused severe neuronal loss, resulting in profound learning and memory deficit. F3.ChAT human NSCs transplanted intracerebroventricularly improved fully the learning and memory function of KA-induced learning deficit animals, in parallel with the elevation of ACh levels in cerebrospinal fluid. F3.ChAT human NSCs migrated to the KA-induced injury site (CA3) and differentiated into neuro...
Hyun B Choi - One of the best experts on this subject based on the ideXlab platform.
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Brain Transplantation of immortalized human neural stem cells promotes functional recovery in mouse intracerebral hemorrhage stroke model
Stem Cells, 2007Co-Authors: Hyun B Choi, In H. Park, Yong Ko, Sang W JeongAbstract:We have generated stable, immortalized cell lines of human NSCs from primary human fetal telencephalon cultures via a retroviral vector encoding v-myc. HB1.F3, one of the human NSC lines, expresses a normal human karyotype of 46, XX, and nestin, a cell type-specific marker for NSCs. F3 has the ability to proliferate continuously and differentiate into cells of neuronal and glial lineage. The HB1.F3 human NSC line was used for cell therapy in a mouse model of intracerebral hemorrhage (ICH) stroke. Experimental ICH was induced in adult mice by intrastriatal administration of bacterial collagenase; 1 week after surgery, the rats were randomly divided into two groups so as to receive intracerebrally either human NSCs labeled with -galactosidase (n 31) or phosphate-buffered saline (PBS) (n 30). Transplanted NSCs were detected by 5-bromo-4-chloro-3indolyl--D-galactoside histochemistry or double labeling with -galactosidase (-gal) and mitogen-activated protein (MAP)2, neurofilaments (both for neurons), or glial fibrillary acidic protein (GFAP) (for astrocytes). Behavior of the animals was evaluated for period up to 8 weeks using modified Rotarod tests and a limb placing test. Transplanted human NSCs were identified in the perihematomal areas and differentiated into neurons (-gal/MAP2 and -gal/ NF) or astrocytes (-gal/GFAP). The NSC-transplanted group showed markedly improved functional performance on the Rotarod test and limb placing after 2–8 weeks compared with the control PBS group (p < .001). These results indicate that the stable immortalized human NSCs are a valuable source of cells for cell replacement and gene transfer for the treatment of ICH and other human neurological disorders. STEM CELLS 2007;25: 1204–1212
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Brain Transplantation of immortalized human neural stem cells promotes functional recovery in mouse intracerebral hemorrhage stroke model
Stem Cells, 2007Co-Authors: Hong J. Lee, Hyun B Choi, Kwang Soo Kim, Eun Ju Kim, Kwang Hoon Lee, In H. ParkAbstract:We have generated stable, immortalized cell lines of human NSCs from primary human fetal telencephalon cultures via a retroviral vector encoding v-myc. HB1.F3, one of the human NSC lines, expresses a normal human karyotype of 46, XX, and nestin, a cell type-specific marker for NSCs. F3 has the ability to proliferate continuously and differentiate into cells of neuronal and glial lineage. The HB1.F3 human NSC line was used for cell therapy in a mouse model of intracerebral hemorrhage (ICH) stroke. Experimental ICH was induced in adult mice by intrastriatal administration of bacterial collagenase; 1 week after surgery, the rats were randomly divided into two groups so as to receive intracerebrally either human NSCs labeled with beta-galactosidase (n = 31) or phosphate-buffered saline (PBS) (n = 30). Transplanted NSCs were detected by 5-bromo-4-chloro-3-indolyl-beta-d-galactoside histochemistry or double labeling with beta-galactosidase (beta-gal) and mitogen-activated protein (MAP)2, neurofilaments (both for neurons), or glial fibrillary acidic protein (GFAP) (for astrocytes). Behavior of the animals was evaluated for period up to 8 weeks using modified Rotarod tests and a limb placing test. Transplanted human NSCs were identified in the perihematomal areas and differentiated into neurons (beta-gal/MAP2(+) and beta-gal/NF(+)) or astrocytes (beta-gal/GFAP(+)). The NSC-transplanted group showed markedly improved functional performance on the Rotarod test and limb placing after 2-8 weeks compared with the control PBS group (p < .001). These results indicate that the stable immortalized human NSCs are a valuable source of cells for cell replacement and gene transfer for the treatment of ICH and other human neurological disorders. Disclosure of potential conflicts of interest is found at the end of this article.