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Jeffery D Kocsis - One of the best experts on this subject based on the ideXlab platform.
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mesenchymal stem cells derived from peripheral blood protects against Ischemia
Journal of Neurotrauma, 2007Co-Authors: Ryo Ukai, Osamu Honmou, Kuniaki Harada, Kiyohiro Houkin, Hirofumi Hamada, Jeffery D KocsisAbstract:Intravenous delivery of mesenchymal stem cells (MSCs) prepared from bone marrow (BMSCs) reduces infarction volume and ameliorates functional deficits in a rat Cerebral Ischemia Model. MSC-like multipotent precursor cells (PMSCs) have also been suggested to exist in peripheral blood. To test the hypothesis that treatment with PMSCs may have a therapeutic benefit in stroke, we compared the efficacy of systemic delivery of BMSCs and PMSCs. A permanent middle Cerebral artery occlusion (MCAO) in rat was induced by intraluminal vascular occlusion with a microfilament. Rat BMSCs and PMSCs were prepared in culture and intravenously injected into the rats 6 h after MCAO. Lesion size was assessed at 6 h, and 1, 3, and 7 days using MR imaging and histology. The hemodynamic change of Cerebral blood perfusion on stroke was assessed the same times using perfusion-weighted image (PWI). Functional outcome was assessed using the treadmill stress test. Both BMSCs and PMSCs treated groups had reduced lesion volume, improved...
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intravenous administration of glial cell line derived neurotrophic factor gene modified human mesenchymal stem cells protects against injury in a Cerebral Ischemia Model in the adult rat
Journal of Neuroscience Research, 2006Co-Authors: Yoshifumi Horita, Osamu Honmou, Kuniaki Harada, Kiyohiro Houkin, Hirofumi Hamada, Jeffery D KocsisAbstract:Intravenous administration of human mesenchymal stem cells (hMSCs) prepared from adult bone marrow has been reported to ameliorate functional deficits after Cerebral artery occlusion in rats. Several hypotheses to account for these therapeutic effects have been suggested, and current thinking is that neuroprotection rather than neurogenesis is responsible. To enhance the therapeutic benefits of hMSCs potentially, we transfected hMSCs with the glial cell line-derived neurotrophic factor (GDNF) gene using a fiber-mutant F/RGD adenovirus vector and investigated whether GDNF gene-modified hMSCs (GDNF-hMSCs) could contribute to functional recovery in a rat permanent middle Cerebral artery occlusion (MCAO) Model. We induced MCAO by using intraluminal vascular occlusion, and GDNF-hMSCs were intravenously infused into the rats 3 hr later. MRI and behavioral analyses revealed that rats receiving GDNF-hMSCs or hMSCs exhibited increased recovery from Ischemia compared with the control group, but the effect was greater in the GDNF-hMSC group. Thus, these results suggest that intravenous administration of hMSCs transfected with the GDNF gene using a fiber-mutant adenovirus vector may be useful in the Cerebral Ischemia and may represent a new strategy for the treatment of stroke.
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intravenous infusion of immortalized human mesenchymal stem cells protects against injury in a Cerebral Ischemia Model in adult rat
Experimental Neurology, 2006Co-Authors: Toshimi Honma, Osamu Honmou, Kuniaki Harada, Kiyohiro Houkin, Hirofumi Hamada, Jeffery D Kocsis, Satoshi IihoshiAbstract:Intravenous infusion of bone marrow cells has demonstrated therapeutic efficacy in animal Models of Cerebral Ischemia and spinal cord injury. We intravenously delivered human mesenchymal stem cells (SH2+, SH3+, CD34−, and CD45−) immortalized with a human-telomerase gene (hTERT-MSCs) and transfected with eGFP or LacZ into rats 12 h after induction of transient middle Cerebral artery occlusion (MCAO), to study their potential therapeutic benefit. hTERT-MSCs were delivered at 12 h after lesion induction. Lesion size was assessed using MR imaging and spectroscopy, and histological methods. Functional outcome was assessed using the Morris water maze and a treadmill test. Intravenous delivery of hTERT-MSCs reduced lesion volume and the magnitude of the reduction and functional improvement was positively correlated with the number of cells injected. The reduction of lesion size could be assessed in vivo with MRI and MRS and was correlated with subsequent histological examination of the brain. This work demonstrates that highly purified hTERT-MSCs reduce Cerebral infarction volume and improve functional outcome.
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i v infusion of brain derived neurotrophic factor gene modified human mesenchymal stem cells protects against injury in a Cerebral Ischemia Model in adult rat
Neuroscience, 2005Co-Authors: T Nomura, Osamu Honmou, Kuniaki Harada, Kiyohiro Houkin, Hirofumi Hamada, Jeffery D KocsisAbstract:Abstract—I.v. delivery of mesenchymal stem cells prepared from adult bone marrow reduces infarction size and ameliorates functional deficits in rat Cerebral Ischemia Models. Administration of the brain-derived neurotrophic factor to the infarction site has also been demonstrated to be neuroprotective. To test the hypothesis that brain-derived neurotrophic factor contributes to the therapeutic benefits of mesenchymal stem cell delivery, we compared the efficacy of systemic delivery of human mesenchymal stem cells and human mesenchymal stem cells transfected with a fiber-mutant F/RGD adenovirus vector with a brain-derived neurotrophic factor gene (brain-derived neurotrophic factor–human mesenchymal stem cells). A permanent middle Cerebral artery occlusion was induced by intraluminal vascular occlusion with a microfilament. Human mesenchymal stem cells and brain-derived neurotrophic factor– human mesenchymal stem cells were i.v. injected into the rats 6 h after middle Cerebral artery occlusion. Lesion size was assessed at 6 h, 1, 3 and 7 days using MR imaging, and histological methods. Functional outcome was assessed using the treadmill stress test. Both human mesenchymal stem cells and brain-derived neurotrophic factor–human mesenchymal stem cells reduced lesion volume and elicited functional improvement compared with the control sham group, but the effect was greater in the brain-derived neurotrophic factor–human mesenchymal stem cell group. ELISA analysis of the infarcted hemisphere revealed an increase in brain-derived neurotrophic factor in the human mesenchymal stem cell groups, but a greater increase in the brain-derived neurotrophic factor–human mesenchymal stem cell group. These data support the hypothesis that brain-derived neurotrophic factor contributes to neuroprotection in Cerebral Ischemia and cellular delivery of brain-derived neurotrophic factor can be achieved by i.v. delivery of human mesenchymal stem cells.
Osamu Honmou - One of the best experts on this subject based on the ideXlab platform.
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mesenchymal stem cells derived from peripheral blood protects against Ischemia
Journal of Neurotrauma, 2007Co-Authors: Ryo Ukai, Osamu Honmou, Kuniaki Harada, Kiyohiro Houkin, Hirofumi Hamada, Jeffery D KocsisAbstract:Intravenous delivery of mesenchymal stem cells (MSCs) prepared from bone marrow (BMSCs) reduces infarction volume and ameliorates functional deficits in a rat Cerebral Ischemia Model. MSC-like multipotent precursor cells (PMSCs) have also been suggested to exist in peripheral blood. To test the hypothesis that treatment with PMSCs may have a therapeutic benefit in stroke, we compared the efficacy of systemic delivery of BMSCs and PMSCs. A permanent middle Cerebral artery occlusion (MCAO) in rat was induced by intraluminal vascular occlusion with a microfilament. Rat BMSCs and PMSCs were prepared in culture and intravenously injected into the rats 6 h after MCAO. Lesion size was assessed at 6 h, and 1, 3, and 7 days using MR imaging and histology. The hemodynamic change of Cerebral blood perfusion on stroke was assessed the same times using perfusion-weighted image (PWI). Functional outcome was assessed using the treadmill stress test. Both BMSCs and PMSCs treated groups had reduced lesion volume, improved...
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intravenous administration of glial cell line derived neurotrophic factor gene modified human mesenchymal stem cells protects against injury in a Cerebral Ischemia Model in the adult rat
Journal of Neuroscience Research, 2006Co-Authors: Yoshifumi Horita, Osamu Honmou, Kuniaki Harada, Kiyohiro Houkin, Hirofumi Hamada, Jeffery D KocsisAbstract:Intravenous administration of human mesenchymal stem cells (hMSCs) prepared from adult bone marrow has been reported to ameliorate functional deficits after Cerebral artery occlusion in rats. Several hypotheses to account for these therapeutic effects have been suggested, and current thinking is that neuroprotection rather than neurogenesis is responsible. To enhance the therapeutic benefits of hMSCs potentially, we transfected hMSCs with the glial cell line-derived neurotrophic factor (GDNF) gene using a fiber-mutant F/RGD adenovirus vector and investigated whether GDNF gene-modified hMSCs (GDNF-hMSCs) could contribute to functional recovery in a rat permanent middle Cerebral artery occlusion (MCAO) Model. We induced MCAO by using intraluminal vascular occlusion, and GDNF-hMSCs were intravenously infused into the rats 3 hr later. MRI and behavioral analyses revealed that rats receiving GDNF-hMSCs or hMSCs exhibited increased recovery from Ischemia compared with the control group, but the effect was greater in the GDNF-hMSC group. Thus, these results suggest that intravenous administration of hMSCs transfected with the GDNF gene using a fiber-mutant adenovirus vector may be useful in the Cerebral Ischemia and may represent a new strategy for the treatment of stroke.
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intravenous infusion of immortalized human mesenchymal stem cells protects against injury in a Cerebral Ischemia Model in adult rat
Experimental Neurology, 2006Co-Authors: Toshimi Honma, Osamu Honmou, Kuniaki Harada, Kiyohiro Houkin, Hirofumi Hamada, Jeffery D Kocsis, Satoshi IihoshiAbstract:Intravenous infusion of bone marrow cells has demonstrated therapeutic efficacy in animal Models of Cerebral Ischemia and spinal cord injury. We intravenously delivered human mesenchymal stem cells (SH2+, SH3+, CD34−, and CD45−) immortalized with a human-telomerase gene (hTERT-MSCs) and transfected with eGFP or LacZ into rats 12 h after induction of transient middle Cerebral artery occlusion (MCAO), to study their potential therapeutic benefit. hTERT-MSCs were delivered at 12 h after lesion induction. Lesion size was assessed using MR imaging and spectroscopy, and histological methods. Functional outcome was assessed using the Morris water maze and a treadmill test. Intravenous delivery of hTERT-MSCs reduced lesion volume and the magnitude of the reduction and functional improvement was positively correlated with the number of cells injected. The reduction of lesion size could be assessed in vivo with MRI and MRS and was correlated with subsequent histological examination of the brain. This work demonstrates that highly purified hTERT-MSCs reduce Cerebral infarction volume and improve functional outcome.
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i v infusion of brain derived neurotrophic factor gene modified human mesenchymal stem cells protects against injury in a Cerebral Ischemia Model in adult rat
Neuroscience, 2005Co-Authors: T Nomura, Osamu Honmou, Kuniaki Harada, Kiyohiro Houkin, Hirofumi Hamada, Jeffery D KocsisAbstract:Abstract—I.v. delivery of mesenchymal stem cells prepared from adult bone marrow reduces infarction size and ameliorates functional deficits in rat Cerebral Ischemia Models. Administration of the brain-derived neurotrophic factor to the infarction site has also been demonstrated to be neuroprotective. To test the hypothesis that brain-derived neurotrophic factor contributes to the therapeutic benefits of mesenchymal stem cell delivery, we compared the efficacy of systemic delivery of human mesenchymal stem cells and human mesenchymal stem cells transfected with a fiber-mutant F/RGD adenovirus vector with a brain-derived neurotrophic factor gene (brain-derived neurotrophic factor–human mesenchymal stem cells). A permanent middle Cerebral artery occlusion was induced by intraluminal vascular occlusion with a microfilament. Human mesenchymal stem cells and brain-derived neurotrophic factor– human mesenchymal stem cells were i.v. injected into the rats 6 h after middle Cerebral artery occlusion. Lesion size was assessed at 6 h, 1, 3 and 7 days using MR imaging, and histological methods. Functional outcome was assessed using the treadmill stress test. Both human mesenchymal stem cells and brain-derived neurotrophic factor–human mesenchymal stem cells reduced lesion volume and elicited functional improvement compared with the control sham group, but the effect was greater in the brain-derived neurotrophic factor–human mesenchymal stem cell group. ELISA analysis of the infarcted hemisphere revealed an increase in brain-derived neurotrophic factor in the human mesenchymal stem cell groups, but a greater increase in the brain-derived neurotrophic factor–human mesenchymal stem cell group. These data support the hypothesis that brain-derived neurotrophic factor contributes to neuroprotection in Cerebral Ischemia and cellular delivery of brain-derived neurotrophic factor can be achieved by i.v. delivery of human mesenchymal stem cells.
Shuhei Yamaguchi - One of the best experts on this subject based on the ideXlab platform.
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human microglia transplanted in rat focal Ischemia brain induce neuroprotection and behavioral improvement
PLOS ONE, 2010Co-Authors: Dashdemberel Narantuya, Abdullah Md Sheikh, Jun'ichi Masuda, Shotai Kobayashi, Atsushi Nagai, Shuhei YamaguchiAbstract:Background and Purpose Microglia are resident immunocompenent and phagocytic cells of central nervous system (CNS), which produce various cytokines and growth factors in response to injury and thereby regulate disease pathology. The purpose of this study is to investigate the effects of microglial transplantation on focal Cerebral Ischemia Model in rat. Methods Transient middle Cerebral artery occlusion (MCAO) in rats was induced by the intraluminal filament technique. HMO6 cells, human microglial cell line, were transplanted intravenously at 48 hours after MCAO. Functional tests were performed and the infarct volume was measured at 7 and 14 days after MCAO. Migration and cell survival of transplanted microglial cells and host glial reaction in the brain were studied by immunohistochemistry. Gene expression of neurotrophic factors, cytokines and chemokines in transplanted cells and host rat glial cells was determined by laser capture microdissection (LCM) and quantitative real time-PCR. Results HMO6 human microglial cells transplantion group demonstrated significant functional recovery compared with control group. At 7 and 14 days after MCAO, infarct volume was significantly reduced in the HMO group. In the HMO6 group, number of apoptotic cells was time-dependently reduced in the infarct core and penumbra. In addition, number of host rat microglia/macrophages and reactive astrocytes was significantly decreased at 7 and 14 days after MCAO in the penumbra. Gene expression of various neurotrophic factors (GDNF, BDNF, VEGF and BMP7) and anti-inflammatory cytokines (IL4 and IL5) was up-regulated in transplanted HMO6 cells of brain tissue compared with those in culture. The expression of GDNF and VEGF in astrocytes in penumbra was significantly up-regulated in the HMO6 group. Conclusions Our results indicate that transplantation of HMO6 human microglial cells reduces ischemic deficits and apoptotic events in stroke animals. The results were mediated by modulation of gliosis and neuroinflammation, and neuroprotection provided by neurotrophic factors of endogenous and transplanted cells-origin.
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transplantation of human mesenchymal stem cells promotes functional improvement and increased expression of neurotrophic factors in a rat focal Cerebral Ischemia Model
Journal of Neuroscience Research, 2009Co-Authors: Kiryo Wakabayashi, Dashdemberel Narantuya, Abdullah Md Sheikh, Yuri Shiota, Tatsuzo Watanabe, Jun'ichi Masuda, Shotai Kobayashi, Atsushi Nagai, Shuhei YamaguchiAbstract:Previous studies have suggested that intravenous transplantation of mesenchymal stem cells (MSCs) in rat Ischemia Models reduces Ischemia-induced brain damage. Here, we analyzed the expression of neurotrophic factors in transplanted human MSCs and host brain tissue in rat middle Cerebral artery occlusion (MCAO) Ischemia Model. At 1 day after transient MCAO, 3 × 106 immortalized human MSC line (B10) cells or PBS was intravenously transplanted. Behavioral tests, infarction volume, and B10 cell migration were investigated at 1, 3, 7, and 14 days after MCAO. The expression of endogenous (rat origin) and exogenous (human origin) neurotorphic factors and cytokines was evaluated by quantitative real-time RT-PCR and Western blot analysis. Compared with PBS controls, rats receiving MSC transplantation showed improved functional recovery and reduced brain infarction volume at 7 and 14 days after MCAO. In MSC-transplanted brain, among many neurotrofic factors, only human insulin-like growth factor 1 (IGF-1) was detected in the core and ischemic border zone at 3 days after MCAO, whereas host cells expressed markedly higher neurotrophic factors (rat origin) than control rats, especially vascular endothelial growth factor (VEGF) at 3 days and epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) at 7 days after MCAO. Intravenously transplanted human MSCs induced functional improvement, reduced infarct volume, and neuroprotection in ischemic rats, possibly by providing IGF-1 and inducing VEGF, EGF, and bFGF neurotrophic factors in host brain. © 2009 Wiley-Liss, Inc.
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transplantation of human mesenchymal stem cells promotes functional improvement and increased expression of neurotrophic factors in a rat focal Cerebral Ischemia Model
Journal of Neuroscience Research, 2009Co-Authors: Kiryo Wakabayashi, Dashdemberel Narantuya, Abdullah Md Sheikh, Yuri Shiota, Tatsuzo Watanabe, Jun'ichi Masuda, Shotai Kobayashi, Atsushi Nagai, Seung U Kim, Shuhei YamaguchiAbstract:Previous studies have suggested that intravenous transplantation of mesenchymal stem cells (MSCs) in rat Ischemia Models reduces Ischemia-induced brain damage. Here, we analyzed the expression of neurotrophic factors in transplanted human MSCs and host brain tissue in rat middle Cerebral artery occlusion (MCAO) Ischemia Model. At 1 day after transient MCAO, 3 x 10(6) immortalized human MSC line (B10) cells or PBS was intravenously transplanted. Behavioral tests, infarction volume, and B10 cell migration were investigated at 1, 3, 7, and 14 days after MCAO. The expression of endogenous (rat origin) and exogenous (human origin) neurotrophic factors and cytokines was evaluated by quantitative real-time RT-PCR and Western blot analysis. Compared with PBS controls, rats receiving MSC transplantation showed improved functional recovery and reduced brain infarction volume at 7 and 14 days after MCAO. In MSC-transplanted brain, among many neurotrophic factors, only human insulin-like growth factor 1 (IGF-1) was detected in the core and ischemic border zone at 3 days after MCAO, whereas host cells expressed markedly higher neurotrophic factors (rat origin) than control rats, especially vascular endothelial growth factor (VEGF) at 3 days and epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) at 7 days after MCAO. Intravenously transplanted human MSCs induced functional improvement, reduced infarct volume, and neuroprotection in ischemic rats, possibly by providing IGF-1 and inducing VEGF, EGF, and bFGF neurotrophic factors in host brain.
Kuniaki Harada - One of the best experts on this subject based on the ideXlab platform.
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mesenchymal stem cells derived from peripheral blood protects against Ischemia
Journal of Neurotrauma, 2007Co-Authors: Ryo Ukai, Osamu Honmou, Kuniaki Harada, Kiyohiro Houkin, Hirofumi Hamada, Jeffery D KocsisAbstract:Intravenous delivery of mesenchymal stem cells (MSCs) prepared from bone marrow (BMSCs) reduces infarction volume and ameliorates functional deficits in a rat Cerebral Ischemia Model. MSC-like multipotent precursor cells (PMSCs) have also been suggested to exist in peripheral blood. To test the hypothesis that treatment with PMSCs may have a therapeutic benefit in stroke, we compared the efficacy of systemic delivery of BMSCs and PMSCs. A permanent middle Cerebral artery occlusion (MCAO) in rat was induced by intraluminal vascular occlusion with a microfilament. Rat BMSCs and PMSCs were prepared in culture and intravenously injected into the rats 6 h after MCAO. Lesion size was assessed at 6 h, and 1, 3, and 7 days using MR imaging and histology. The hemodynamic change of Cerebral blood perfusion on stroke was assessed the same times using perfusion-weighted image (PWI). Functional outcome was assessed using the treadmill stress test. Both BMSCs and PMSCs treated groups had reduced lesion volume, improved...
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intravenous administration of glial cell line derived neurotrophic factor gene modified human mesenchymal stem cells protects against injury in a Cerebral Ischemia Model in the adult rat
Journal of Neuroscience Research, 2006Co-Authors: Yoshifumi Horita, Osamu Honmou, Kuniaki Harada, Kiyohiro Houkin, Hirofumi Hamada, Jeffery D KocsisAbstract:Intravenous administration of human mesenchymal stem cells (hMSCs) prepared from adult bone marrow has been reported to ameliorate functional deficits after Cerebral artery occlusion in rats. Several hypotheses to account for these therapeutic effects have been suggested, and current thinking is that neuroprotection rather than neurogenesis is responsible. To enhance the therapeutic benefits of hMSCs potentially, we transfected hMSCs with the glial cell line-derived neurotrophic factor (GDNF) gene using a fiber-mutant F/RGD adenovirus vector and investigated whether GDNF gene-modified hMSCs (GDNF-hMSCs) could contribute to functional recovery in a rat permanent middle Cerebral artery occlusion (MCAO) Model. We induced MCAO by using intraluminal vascular occlusion, and GDNF-hMSCs were intravenously infused into the rats 3 hr later. MRI and behavioral analyses revealed that rats receiving GDNF-hMSCs or hMSCs exhibited increased recovery from Ischemia compared with the control group, but the effect was greater in the GDNF-hMSC group. Thus, these results suggest that intravenous administration of hMSCs transfected with the GDNF gene using a fiber-mutant adenovirus vector may be useful in the Cerebral Ischemia and may represent a new strategy for the treatment of stroke.
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intravenous infusion of immortalized human mesenchymal stem cells protects against injury in a Cerebral Ischemia Model in adult rat
Experimental Neurology, 2006Co-Authors: Toshimi Honma, Osamu Honmou, Kuniaki Harada, Kiyohiro Houkin, Hirofumi Hamada, Jeffery D Kocsis, Satoshi IihoshiAbstract:Intravenous infusion of bone marrow cells has demonstrated therapeutic efficacy in animal Models of Cerebral Ischemia and spinal cord injury. We intravenously delivered human mesenchymal stem cells (SH2+, SH3+, CD34−, and CD45−) immortalized with a human-telomerase gene (hTERT-MSCs) and transfected with eGFP or LacZ into rats 12 h after induction of transient middle Cerebral artery occlusion (MCAO), to study their potential therapeutic benefit. hTERT-MSCs were delivered at 12 h after lesion induction. Lesion size was assessed using MR imaging and spectroscopy, and histological methods. Functional outcome was assessed using the Morris water maze and a treadmill test. Intravenous delivery of hTERT-MSCs reduced lesion volume and the magnitude of the reduction and functional improvement was positively correlated with the number of cells injected. The reduction of lesion size could be assessed in vivo with MRI and MRS and was correlated with subsequent histological examination of the brain. This work demonstrates that highly purified hTERT-MSCs reduce Cerebral infarction volume and improve functional outcome.
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i v infusion of brain derived neurotrophic factor gene modified human mesenchymal stem cells protects against injury in a Cerebral Ischemia Model in adult rat
Neuroscience, 2005Co-Authors: T Nomura, Osamu Honmou, Kuniaki Harada, Kiyohiro Houkin, Hirofumi Hamada, Jeffery D KocsisAbstract:Abstract—I.v. delivery of mesenchymal stem cells prepared from adult bone marrow reduces infarction size and ameliorates functional deficits in rat Cerebral Ischemia Models. Administration of the brain-derived neurotrophic factor to the infarction site has also been demonstrated to be neuroprotective. To test the hypothesis that brain-derived neurotrophic factor contributes to the therapeutic benefits of mesenchymal stem cell delivery, we compared the efficacy of systemic delivery of human mesenchymal stem cells and human mesenchymal stem cells transfected with a fiber-mutant F/RGD adenovirus vector with a brain-derived neurotrophic factor gene (brain-derived neurotrophic factor–human mesenchymal stem cells). A permanent middle Cerebral artery occlusion was induced by intraluminal vascular occlusion with a microfilament. Human mesenchymal stem cells and brain-derived neurotrophic factor– human mesenchymal stem cells were i.v. injected into the rats 6 h after middle Cerebral artery occlusion. Lesion size was assessed at 6 h, 1, 3 and 7 days using MR imaging, and histological methods. Functional outcome was assessed using the treadmill stress test. Both human mesenchymal stem cells and brain-derived neurotrophic factor–human mesenchymal stem cells reduced lesion volume and elicited functional improvement compared with the control sham group, but the effect was greater in the brain-derived neurotrophic factor–human mesenchymal stem cell group. ELISA analysis of the infarcted hemisphere revealed an increase in brain-derived neurotrophic factor in the human mesenchymal stem cell groups, but a greater increase in the brain-derived neurotrophic factor–human mesenchymal stem cell group. These data support the hypothesis that brain-derived neurotrophic factor contributes to neuroprotection in Cerebral Ischemia and cellular delivery of brain-derived neurotrophic factor can be achieved by i.v. delivery of human mesenchymal stem cells.
Kiyohiro Houkin - One of the best experts on this subject based on the ideXlab platform.
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mesenchymal stem cells derived from peripheral blood protects against Ischemia
Journal of Neurotrauma, 2007Co-Authors: Ryo Ukai, Osamu Honmou, Kuniaki Harada, Kiyohiro Houkin, Hirofumi Hamada, Jeffery D KocsisAbstract:Intravenous delivery of mesenchymal stem cells (MSCs) prepared from bone marrow (BMSCs) reduces infarction volume and ameliorates functional deficits in a rat Cerebral Ischemia Model. MSC-like multipotent precursor cells (PMSCs) have also been suggested to exist in peripheral blood. To test the hypothesis that treatment with PMSCs may have a therapeutic benefit in stroke, we compared the efficacy of systemic delivery of BMSCs and PMSCs. A permanent middle Cerebral artery occlusion (MCAO) in rat was induced by intraluminal vascular occlusion with a microfilament. Rat BMSCs and PMSCs were prepared in culture and intravenously injected into the rats 6 h after MCAO. Lesion size was assessed at 6 h, and 1, 3, and 7 days using MR imaging and histology. The hemodynamic change of Cerebral blood perfusion on stroke was assessed the same times using perfusion-weighted image (PWI). Functional outcome was assessed using the treadmill stress test. Both BMSCs and PMSCs treated groups had reduced lesion volume, improved...
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intravenous administration of glial cell line derived neurotrophic factor gene modified human mesenchymal stem cells protects against injury in a Cerebral Ischemia Model in the adult rat
Journal of Neuroscience Research, 2006Co-Authors: Yoshifumi Horita, Osamu Honmou, Kuniaki Harada, Kiyohiro Houkin, Hirofumi Hamada, Jeffery D KocsisAbstract:Intravenous administration of human mesenchymal stem cells (hMSCs) prepared from adult bone marrow has been reported to ameliorate functional deficits after Cerebral artery occlusion in rats. Several hypotheses to account for these therapeutic effects have been suggested, and current thinking is that neuroprotection rather than neurogenesis is responsible. To enhance the therapeutic benefits of hMSCs potentially, we transfected hMSCs with the glial cell line-derived neurotrophic factor (GDNF) gene using a fiber-mutant F/RGD adenovirus vector and investigated whether GDNF gene-modified hMSCs (GDNF-hMSCs) could contribute to functional recovery in a rat permanent middle Cerebral artery occlusion (MCAO) Model. We induced MCAO by using intraluminal vascular occlusion, and GDNF-hMSCs were intravenously infused into the rats 3 hr later. MRI and behavioral analyses revealed that rats receiving GDNF-hMSCs or hMSCs exhibited increased recovery from Ischemia compared with the control group, but the effect was greater in the GDNF-hMSC group. Thus, these results suggest that intravenous administration of hMSCs transfected with the GDNF gene using a fiber-mutant adenovirus vector may be useful in the Cerebral Ischemia and may represent a new strategy for the treatment of stroke.
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intravenous infusion of immortalized human mesenchymal stem cells protects against injury in a Cerebral Ischemia Model in adult rat
Experimental Neurology, 2006Co-Authors: Toshimi Honma, Osamu Honmou, Kuniaki Harada, Kiyohiro Houkin, Hirofumi Hamada, Jeffery D Kocsis, Satoshi IihoshiAbstract:Intravenous infusion of bone marrow cells has demonstrated therapeutic efficacy in animal Models of Cerebral Ischemia and spinal cord injury. We intravenously delivered human mesenchymal stem cells (SH2+, SH3+, CD34−, and CD45−) immortalized with a human-telomerase gene (hTERT-MSCs) and transfected with eGFP or LacZ into rats 12 h after induction of transient middle Cerebral artery occlusion (MCAO), to study their potential therapeutic benefit. hTERT-MSCs were delivered at 12 h after lesion induction. Lesion size was assessed using MR imaging and spectroscopy, and histological methods. Functional outcome was assessed using the Morris water maze and a treadmill test. Intravenous delivery of hTERT-MSCs reduced lesion volume and the magnitude of the reduction and functional improvement was positively correlated with the number of cells injected. The reduction of lesion size could be assessed in vivo with MRI and MRS and was correlated with subsequent histological examination of the brain. This work demonstrates that highly purified hTERT-MSCs reduce Cerebral infarction volume and improve functional outcome.
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i v infusion of brain derived neurotrophic factor gene modified human mesenchymal stem cells protects against injury in a Cerebral Ischemia Model in adult rat
Neuroscience, 2005Co-Authors: T Nomura, Osamu Honmou, Kuniaki Harada, Kiyohiro Houkin, Hirofumi Hamada, Jeffery D KocsisAbstract:Abstract—I.v. delivery of mesenchymal stem cells prepared from adult bone marrow reduces infarction size and ameliorates functional deficits in rat Cerebral Ischemia Models. Administration of the brain-derived neurotrophic factor to the infarction site has also been demonstrated to be neuroprotective. To test the hypothesis that brain-derived neurotrophic factor contributes to the therapeutic benefits of mesenchymal stem cell delivery, we compared the efficacy of systemic delivery of human mesenchymal stem cells and human mesenchymal stem cells transfected with a fiber-mutant F/RGD adenovirus vector with a brain-derived neurotrophic factor gene (brain-derived neurotrophic factor–human mesenchymal stem cells). A permanent middle Cerebral artery occlusion was induced by intraluminal vascular occlusion with a microfilament. Human mesenchymal stem cells and brain-derived neurotrophic factor– human mesenchymal stem cells were i.v. injected into the rats 6 h after middle Cerebral artery occlusion. Lesion size was assessed at 6 h, 1, 3 and 7 days using MR imaging, and histological methods. Functional outcome was assessed using the treadmill stress test. Both human mesenchymal stem cells and brain-derived neurotrophic factor–human mesenchymal stem cells reduced lesion volume and elicited functional improvement compared with the control sham group, but the effect was greater in the brain-derived neurotrophic factor–human mesenchymal stem cell group. ELISA analysis of the infarcted hemisphere revealed an increase in brain-derived neurotrophic factor in the human mesenchymal stem cell groups, but a greater increase in the brain-derived neurotrophic factor–human mesenchymal stem cell group. These data support the hypothesis that brain-derived neurotrophic factor contributes to neuroprotection in Cerebral Ischemia and cellular delivery of brain-derived neurotrophic factor can be achieved by i.v. delivery of human mesenchymal stem cells.