Intranasal Delivery of Bone Marrow Stromal Cells Preconditioned with Fasudil to Treat a Mouse Model of Parkinson’s Disease
Yilin Tang,1,* Linlin Han,1,* Xiaochen Bai,1,2 Xiaoniu Liang,1 Jue Zhao,1 Fang Huang,2 Jian Wang1 1Department of Neurology and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of China; 2The State Key Laborator...
Ausführliche Beschreibung
Autor*in: |
Tang Y [verfasserIn] Han L [verfasserIn] Bai X [verfasserIn] Liang X [verfasserIn] Zhao J [verfasserIn] Huang F [verfasserIn] Wang J [verfasserIn] |
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2020 |
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In: Neuropsychiatric Disease and Treatment - Dove Medical Press, 2009, (2020), Seite 249-262 |
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year:2020 ; pages:249-262 |
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DOAJ063352842 |
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(DE-627)DOAJ063352842 (DE-599)DOAJ5036371533804482b9575c434ece3bac DE-627 ger DE-627 rakwb eng RC321-571 RC346-429 Tang Y verfasserin aut Intranasal Delivery of Bone Marrow Stromal Cells Preconditioned with Fasudil to Treat a Mouse Model of Parkinson’s Disease 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Yilin Tang,1,* Linlin Han,1,* Xiaochen Bai,1,2 Xiaoniu Liang,1 Jue Zhao,1 Fang Huang,2 Jian Wang1 1Department of Neurology and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of China; 2The State Key Laboratory of Medical Neurobiology, The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian WangDepartment of Neurology and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of ChinaTel +86-133 2193 4789Fax +86-21-5288 8163Email wangjian336hotmail.comObjective: Stem cell transplantation is a promising strategy with great potential to treat Parkinson’s disease (PD). Nevertheless, improving the cell delivery route and optimising implanted cells are necessary to increase the therapeutic effect. Herein, we investigated whether intranasal delivery of bone marrow stromal cells (BMSCs) has beneficial effects in a PD mouse model and whether the therapeutic potential of BMSCs could be enhanced by preconditioning with fasudil.Methods: A PD mouse model was developed by intraperitoneally administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice were treated intranasally with phosphate buffered saline (PBS), BMSCs, or BMSCs preconditioned with fasudil. One month later, the effects of BMSC treatment were analysed.Results: Our study showed that fasudil could accelerate the proliferation of BMSCs and promote brain-derived neurotrophic factor (BDNF) secretion in vitro. Intranasally administered BMSCs were capable of surviving and migrating in the brain. Intranasal delivery of BMSCs preconditioned with fasudil significantly improved motor function and reduced dopaminergic neuron loss in substantia nigra; treatment with BMSCs and PBS resulted in similar outcomes. Preconditioning with fasudil inhibited the activation and aggregation of microglia, suppressed immune response, and reinforced BDNF secretion in MPTP-PD mice significantly more than treatment with BMSCs alone.Conclusion: The present study demonstrates that intranasally administering BMSCs preconditioned with fasudil is a promising cell-based therapy for PD.Keywords: Parkinson’s disease, intranasal delivery, bone marrow stromal cells, fasudil parkinson’s disease intranasal delivery bone marrow stromal cells fasudil Neurosciences. Biological psychiatry. Neuropsychiatry Neurology. Diseases of the nervous system Han L verfasserin aut Bai X verfasserin aut Liang X verfasserin aut Zhao J verfasserin aut Huang F verfasserin aut Wang J verfasserin aut In Neuropsychiatric Disease and Treatment Dove Medical Press, 2009 (2020), Seite 249-262 (DE-627)481905693 (DE-600)2180554-4 11782021 nnns year:2020 pages:249-262 https://doaj.org/article/5036371533804482b9575c434ece3bac kostenfrei https://www.dovepress.com/intranasal-delivery-of-bone-marrow-stromal-cells-preconditioned-with-f-peer-reviewed-article-NDT kostenfrei https://doaj.org/toc/1178-2021 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2020 249-262 |
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(DE-627)DOAJ063352842 (DE-599)DOAJ5036371533804482b9575c434ece3bac DE-627 ger DE-627 rakwb eng RC321-571 RC346-429 Tang Y verfasserin aut Intranasal Delivery of Bone Marrow Stromal Cells Preconditioned with Fasudil to Treat a Mouse Model of Parkinson’s Disease 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Yilin Tang,1,* Linlin Han,1,* Xiaochen Bai,1,2 Xiaoniu Liang,1 Jue Zhao,1 Fang Huang,2 Jian Wang1 1Department of Neurology and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of China; 2The State Key Laboratory of Medical Neurobiology, The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian WangDepartment of Neurology and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of ChinaTel +86-133 2193 4789Fax +86-21-5288 8163Email wangjian336hotmail.comObjective: Stem cell transplantation is a promising strategy with great potential to treat Parkinson’s disease (PD). Nevertheless, improving the cell delivery route and optimising implanted cells are necessary to increase the therapeutic effect. Herein, we investigated whether intranasal delivery of bone marrow stromal cells (BMSCs) has beneficial effects in a PD mouse model and whether the therapeutic potential of BMSCs could be enhanced by preconditioning with fasudil.Methods: A PD mouse model was developed by intraperitoneally administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice were treated intranasally with phosphate buffered saline (PBS), BMSCs, or BMSCs preconditioned with fasudil. One month later, the effects of BMSC treatment were analysed.Results: Our study showed that fasudil could accelerate the proliferation of BMSCs and promote brain-derived neurotrophic factor (BDNF) secretion in vitro. Intranasally administered BMSCs were capable of surviving and migrating in the brain. Intranasal delivery of BMSCs preconditioned with fasudil significantly improved motor function and reduced dopaminergic neuron loss in substantia nigra; treatment with BMSCs and PBS resulted in similar outcomes. Preconditioning with fasudil inhibited the activation and aggregation of microglia, suppressed immune response, and reinforced BDNF secretion in MPTP-PD mice significantly more than treatment with BMSCs alone.Conclusion: The present study demonstrates that intranasally administering BMSCs preconditioned with fasudil is a promising cell-based therapy for PD.Keywords: Parkinson’s disease, intranasal delivery, bone marrow stromal cells, fasudil parkinson’s disease intranasal delivery bone marrow stromal cells fasudil Neurosciences. Biological psychiatry. Neuropsychiatry Neurology. Diseases of the nervous system Han L verfasserin aut Bai X verfasserin aut Liang X verfasserin aut Zhao J verfasserin aut Huang F verfasserin aut Wang J verfasserin aut In Neuropsychiatric Disease and Treatment Dove Medical Press, 2009 (2020), Seite 249-262 (DE-627)481905693 (DE-600)2180554-4 11782021 nnns year:2020 pages:249-262 https://doaj.org/article/5036371533804482b9575c434ece3bac kostenfrei https://www.dovepress.com/intranasal-delivery-of-bone-marrow-stromal-cells-preconditioned-with-f-peer-reviewed-article-NDT kostenfrei https://doaj.org/toc/1178-2021 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2020 249-262 |
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(DE-627)DOAJ063352842 (DE-599)DOAJ5036371533804482b9575c434ece3bac DE-627 ger DE-627 rakwb eng RC321-571 RC346-429 Tang Y verfasserin aut Intranasal Delivery of Bone Marrow Stromal Cells Preconditioned with Fasudil to Treat a Mouse Model of Parkinson’s Disease 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Yilin Tang,1,* Linlin Han,1,* Xiaochen Bai,1,2 Xiaoniu Liang,1 Jue Zhao,1 Fang Huang,2 Jian Wang1 1Department of Neurology and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of China; 2The State Key Laboratory of Medical Neurobiology, The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian WangDepartment of Neurology and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of ChinaTel +86-133 2193 4789Fax +86-21-5288 8163Email wangjian336hotmail.comObjective: Stem cell transplantation is a promising strategy with great potential to treat Parkinson’s disease (PD). Nevertheless, improving the cell delivery route and optimising implanted cells are necessary to increase the therapeutic effect. Herein, we investigated whether intranasal delivery of bone marrow stromal cells (BMSCs) has beneficial effects in a PD mouse model and whether the therapeutic potential of BMSCs could be enhanced by preconditioning with fasudil.Methods: A PD mouse model was developed by intraperitoneally administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice were treated intranasally with phosphate buffered saline (PBS), BMSCs, or BMSCs preconditioned with fasudil. One month later, the effects of BMSC treatment were analysed.Results: Our study showed that fasudil could accelerate the proliferation of BMSCs and promote brain-derived neurotrophic factor (BDNF) secretion in vitro. Intranasally administered BMSCs were capable of surviving and migrating in the brain. Intranasal delivery of BMSCs preconditioned with fasudil significantly improved motor function and reduced dopaminergic neuron loss in substantia nigra; treatment with BMSCs and PBS resulted in similar outcomes. Preconditioning with fasudil inhibited the activation and aggregation of microglia, suppressed immune response, and reinforced BDNF secretion in MPTP-PD mice significantly more than treatment with BMSCs alone.Conclusion: The present study demonstrates that intranasally administering BMSCs preconditioned with fasudil is a promising cell-based therapy for PD.Keywords: Parkinson’s disease, intranasal delivery, bone marrow stromal cells, fasudil parkinson’s disease intranasal delivery bone marrow stromal cells fasudil Neurosciences. Biological psychiatry. Neuropsychiatry Neurology. Diseases of the nervous system Han L verfasserin aut Bai X verfasserin aut Liang X verfasserin aut Zhao J verfasserin aut Huang F verfasserin aut Wang J verfasserin aut In Neuropsychiatric Disease and Treatment Dove Medical Press, 2009 (2020), Seite 249-262 (DE-627)481905693 (DE-600)2180554-4 11782021 nnns year:2020 pages:249-262 https://doaj.org/article/5036371533804482b9575c434ece3bac kostenfrei https://www.dovepress.com/intranasal-delivery-of-bone-marrow-stromal-cells-preconditioned-with-f-peer-reviewed-article-NDT kostenfrei https://doaj.org/toc/1178-2021 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2020 249-262 |
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(DE-627)DOAJ063352842 (DE-599)DOAJ5036371533804482b9575c434ece3bac DE-627 ger DE-627 rakwb eng RC321-571 RC346-429 Tang Y verfasserin aut Intranasal Delivery of Bone Marrow Stromal Cells Preconditioned with Fasudil to Treat a Mouse Model of Parkinson’s Disease 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Yilin Tang,1,* Linlin Han,1,* Xiaochen Bai,1,2 Xiaoniu Liang,1 Jue Zhao,1 Fang Huang,2 Jian Wang1 1Department of Neurology and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of China; 2The State Key Laboratory of Medical Neurobiology, The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian WangDepartment of Neurology and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of ChinaTel +86-133 2193 4789Fax +86-21-5288 8163Email wangjian336hotmail.comObjective: Stem cell transplantation is a promising strategy with great potential to treat Parkinson’s disease (PD). Nevertheless, improving the cell delivery route and optimising implanted cells are necessary to increase the therapeutic effect. Herein, we investigated whether intranasal delivery of bone marrow stromal cells (BMSCs) has beneficial effects in a PD mouse model and whether the therapeutic potential of BMSCs could be enhanced by preconditioning with fasudil.Methods: A PD mouse model was developed by intraperitoneally administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice were treated intranasally with phosphate buffered saline (PBS), BMSCs, or BMSCs preconditioned with fasudil. One month later, the effects of BMSC treatment were analysed.Results: Our study showed that fasudil could accelerate the proliferation of BMSCs and promote brain-derived neurotrophic factor (BDNF) secretion in vitro. Intranasally administered BMSCs were capable of surviving and migrating in the brain. Intranasal delivery of BMSCs preconditioned with fasudil significantly improved motor function and reduced dopaminergic neuron loss in substantia nigra; treatment with BMSCs and PBS resulted in similar outcomes. Preconditioning with fasudil inhibited the activation and aggregation of microglia, suppressed immune response, and reinforced BDNF secretion in MPTP-PD mice significantly more than treatment with BMSCs alone.Conclusion: The present study demonstrates that intranasally administering BMSCs preconditioned with fasudil is a promising cell-based therapy for PD.Keywords: Parkinson’s disease, intranasal delivery, bone marrow stromal cells, fasudil parkinson’s disease intranasal delivery bone marrow stromal cells fasudil Neurosciences. Biological psychiatry. Neuropsychiatry Neurology. Diseases of the nervous system Han L verfasserin aut Bai X verfasserin aut Liang X verfasserin aut Zhao J verfasserin aut Huang F verfasserin aut Wang J verfasserin aut In Neuropsychiatric Disease and Treatment Dove Medical Press, 2009 (2020), Seite 249-262 (DE-627)481905693 (DE-600)2180554-4 11782021 nnns year:2020 pages:249-262 https://doaj.org/article/5036371533804482b9575c434ece3bac kostenfrei https://www.dovepress.com/intranasal-delivery-of-bone-marrow-stromal-cells-preconditioned-with-f-peer-reviewed-article-NDT kostenfrei https://doaj.org/toc/1178-2021 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2020 249-262 |
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(DE-627)DOAJ063352842 (DE-599)DOAJ5036371533804482b9575c434ece3bac DE-627 ger DE-627 rakwb eng RC321-571 RC346-429 Tang Y verfasserin aut Intranasal Delivery of Bone Marrow Stromal Cells Preconditioned with Fasudil to Treat a Mouse Model of Parkinson’s Disease 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Yilin Tang,1,* Linlin Han,1,* Xiaochen Bai,1,2 Xiaoniu Liang,1 Jue Zhao,1 Fang Huang,2 Jian Wang1 1Department of Neurology and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of China; 2The State Key Laboratory of Medical Neurobiology, The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian WangDepartment of Neurology and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of ChinaTel +86-133 2193 4789Fax +86-21-5288 8163Email wangjian336hotmail.comObjective: Stem cell transplantation is a promising strategy with great potential to treat Parkinson’s disease (PD). Nevertheless, improving the cell delivery route and optimising implanted cells are necessary to increase the therapeutic effect. Herein, we investigated whether intranasal delivery of bone marrow stromal cells (BMSCs) has beneficial effects in a PD mouse model and whether the therapeutic potential of BMSCs could be enhanced by preconditioning with fasudil.Methods: A PD mouse model was developed by intraperitoneally administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice were treated intranasally with phosphate buffered saline (PBS), BMSCs, or BMSCs preconditioned with fasudil. One month later, the effects of BMSC treatment were analysed.Results: Our study showed that fasudil could accelerate the proliferation of BMSCs and promote brain-derived neurotrophic factor (BDNF) secretion in vitro. Intranasally administered BMSCs were capable of surviving and migrating in the brain. Intranasal delivery of BMSCs preconditioned with fasudil significantly improved motor function and reduced dopaminergic neuron loss in substantia nigra; treatment with BMSCs and PBS resulted in similar outcomes. Preconditioning with fasudil inhibited the activation and aggregation of microglia, suppressed immune response, and reinforced BDNF secretion in MPTP-PD mice significantly more than treatment with BMSCs alone.Conclusion: The present study demonstrates that intranasally administering BMSCs preconditioned with fasudil is a promising cell-based therapy for PD.Keywords: Parkinson’s disease, intranasal delivery, bone marrow stromal cells, fasudil parkinson’s disease intranasal delivery bone marrow stromal cells fasudil Neurosciences. Biological psychiatry. Neuropsychiatry Neurology. Diseases of the nervous system Han L verfasserin aut Bai X verfasserin aut Liang X verfasserin aut Zhao J verfasserin aut Huang F verfasserin aut Wang J verfasserin aut In Neuropsychiatric Disease and Treatment Dove Medical Press, 2009 (2020), Seite 249-262 (DE-627)481905693 (DE-600)2180554-4 11782021 nnns year:2020 pages:249-262 https://doaj.org/article/5036371533804482b9575c434ece3bac kostenfrei https://www.dovepress.com/intranasal-delivery-of-bone-marrow-stromal-cells-preconditioned-with-f-peer-reviewed-article-NDT kostenfrei https://doaj.org/toc/1178-2021 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2020 249-262 |
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Intranasal Delivery of Bone Marrow Stromal Cells Preconditioned with Fasudil to Treat a Mouse Model of Parkinson’s Disease |
abstract |
Yilin Tang,1,* Linlin Han,1,* Xiaochen Bai,1,2 Xiaoniu Liang,1 Jue Zhao,1 Fang Huang,2 Jian Wang1 1Department of Neurology and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of China; 2The State Key Laboratory of Medical Neurobiology, The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian WangDepartment of Neurology and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of ChinaTel +86-133 2193 4789Fax +86-21-5288 8163Email wangjian336hotmail.comObjective: Stem cell transplantation is a promising strategy with great potential to treat Parkinson’s disease (PD). Nevertheless, improving the cell delivery route and optimising implanted cells are necessary to increase the therapeutic effect. Herein, we investigated whether intranasal delivery of bone marrow stromal cells (BMSCs) has beneficial effects in a PD mouse model and whether the therapeutic potential of BMSCs could be enhanced by preconditioning with fasudil.Methods: A PD mouse model was developed by intraperitoneally administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice were treated intranasally with phosphate buffered saline (PBS), BMSCs, or BMSCs preconditioned with fasudil. One month later, the effects of BMSC treatment were analysed.Results: Our study showed that fasudil could accelerate the proliferation of BMSCs and promote brain-derived neurotrophic factor (BDNF) secretion in vitro. Intranasally administered BMSCs were capable of surviving and migrating in the brain. Intranasal delivery of BMSCs preconditioned with fasudil significantly improved motor function and reduced dopaminergic neuron loss in substantia nigra; treatment with BMSCs and PBS resulted in similar outcomes. Preconditioning with fasudil inhibited the activation and aggregation of microglia, suppressed immune response, and reinforced BDNF secretion in MPTP-PD mice significantly more than treatment with BMSCs alone.Conclusion: The present study demonstrates that intranasally administering BMSCs preconditioned with fasudil is a promising cell-based therapy for PD.Keywords: Parkinson’s disease, intranasal delivery, bone marrow stromal cells, fasudil |
abstractGer |
Yilin Tang,1,* Linlin Han,1,* Xiaochen Bai,1,2 Xiaoniu Liang,1 Jue Zhao,1 Fang Huang,2 Jian Wang1 1Department of Neurology and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of China; 2The State Key Laboratory of Medical Neurobiology, The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian WangDepartment of Neurology and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of ChinaTel +86-133 2193 4789Fax +86-21-5288 8163Email wangjian336hotmail.comObjective: Stem cell transplantation is a promising strategy with great potential to treat Parkinson’s disease (PD). Nevertheless, improving the cell delivery route and optimising implanted cells are necessary to increase the therapeutic effect. Herein, we investigated whether intranasal delivery of bone marrow stromal cells (BMSCs) has beneficial effects in a PD mouse model and whether the therapeutic potential of BMSCs could be enhanced by preconditioning with fasudil.Methods: A PD mouse model was developed by intraperitoneally administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice were treated intranasally with phosphate buffered saline (PBS), BMSCs, or BMSCs preconditioned with fasudil. One month later, the effects of BMSC treatment were analysed.Results: Our study showed that fasudil could accelerate the proliferation of BMSCs and promote brain-derived neurotrophic factor (BDNF) secretion in vitro. Intranasally administered BMSCs were capable of surviving and migrating in the brain. Intranasal delivery of BMSCs preconditioned with fasudil significantly improved motor function and reduced dopaminergic neuron loss in substantia nigra; treatment with BMSCs and PBS resulted in similar outcomes. Preconditioning with fasudil inhibited the activation and aggregation of microglia, suppressed immune response, and reinforced BDNF secretion in MPTP-PD mice significantly more than treatment with BMSCs alone.Conclusion: The present study demonstrates that intranasally administering BMSCs preconditioned with fasudil is a promising cell-based therapy for PD.Keywords: Parkinson’s disease, intranasal delivery, bone marrow stromal cells, fasudil |
abstract_unstemmed |
Yilin Tang,1,* Linlin Han,1,* Xiaochen Bai,1,2 Xiaoniu Liang,1 Jue Zhao,1 Fang Huang,2 Jian Wang1 1Department of Neurology and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of China; 2The State Key Laboratory of Medical Neurobiology, The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian WangDepartment of Neurology and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of ChinaTel +86-133 2193 4789Fax +86-21-5288 8163Email wangjian336hotmail.comObjective: Stem cell transplantation is a promising strategy with great potential to treat Parkinson’s disease (PD). Nevertheless, improving the cell delivery route and optimising implanted cells are necessary to increase the therapeutic effect. Herein, we investigated whether intranasal delivery of bone marrow stromal cells (BMSCs) has beneficial effects in a PD mouse model and whether the therapeutic potential of BMSCs could be enhanced by preconditioning with fasudil.Methods: A PD mouse model was developed by intraperitoneally administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice were treated intranasally with phosphate buffered saline (PBS), BMSCs, or BMSCs preconditioned with fasudil. One month later, the effects of BMSC treatment were analysed.Results: Our study showed that fasudil could accelerate the proliferation of BMSCs and promote brain-derived neurotrophic factor (BDNF) secretion in vitro. Intranasally administered BMSCs were capable of surviving and migrating in the brain. Intranasal delivery of BMSCs preconditioned with fasudil significantly improved motor function and reduced dopaminergic neuron loss in substantia nigra; treatment with BMSCs and PBS resulted in similar outcomes. Preconditioning with fasudil inhibited the activation and aggregation of microglia, suppressed immune response, and reinforced BDNF secretion in MPTP-PD mice significantly more than treatment with BMSCs alone.Conclusion: The present study demonstrates that intranasally administering BMSCs preconditioned with fasudil is a promising cell-based therapy for PD.Keywords: Parkinson’s disease, intranasal delivery, bone marrow stromal cells, fasudil |
collection_details |
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title_short |
Intranasal Delivery of Bone Marrow Stromal Cells Preconditioned with Fasudil to Treat a Mouse Model of Parkinson’s Disease |
url |
https://doaj.org/article/5036371533804482b9575c434ece3bac https://www.dovepress.com/intranasal-delivery-of-bone-marrow-stromal-cells-preconditioned-with-f-peer-reviewed-article-NDT https://doaj.org/toc/1178-2021 |
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