Intermittent, low dose carbon monoxide exposure enhances survival and dopaminergic differentiation of human neural stem cells
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10362/30670 |
Resumo: | Exploratory studies using human fetal tissue have suggested that intrastriatal transplantation of dopaminergic neurons may become a future treatment for patients with Parkinson’s disease. However, the use of human fetal tissue is compromised by ethical, regulatory and practical concerns. Human stem cells constitute an alternative source of cells for transplantation in Parkinson’s disease, but efficient protocols for controlled dopaminergic differentiation need to be developed. Short-term, low-level carbon monoxide (CO) exposure has been shown to affect signaling in several tissues, resulting in both protection and generation of reactive oxygen species. The present study investigated the effect of CO produced by a novel CO-releasing molecule on dopaminergic differentiation of human neural stem cells. Short-term exposure to 25 ppm CO at days 0 and 4 significantly increased the relative content of β-tubulin III-immunoreactive immature neurons and tyrosine hydroxylase expressing catecholaminergic neurons, as assessed 6 days after differentiation. Also the number of microtubule associated protein 2-positive mature neurons had increased significantly. Moreover, the content of apoptotic cells (Caspase3) was reduced, whereas the expression of a cell proliferation marker (Ki67) was left unchanged. Increased expression of hypoxia inducible factor-1α and production of reactive oxygen species (ROS) in cultures exposed to CO may suggest a mechanism involving mitochondrial alterations and generation of ROS. In conclusion, the present procedure using controlled, short-term CO exposure allows efficient dopaminergic differentiation of human neural stem cells at low cost and may as such be useful for derivation of cells for experimental studies and future development of donor cells for transplantation in Parkinson’s disease. |
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Intermittent, low dose carbon monoxide exposure enhances survival and dopaminergic differentiation of human neural stem cellsHEME OXYGENASE 1FETAL NIGRAL TRANSPLANTATIONHYPOXIA-INDUCIBLE FACTOR-1ENDOTHELIAL GROWTH-FACTORPARKINSONS-DISEASENEURONAL DIFFERENTIATIONISCHEMIA/REPERFUSION INJURYINFLAMMATORY RESPONSESIGNALING PATHWAYSMOLECULE-2 CORM-2SDG 3 - Good Health and Well-beingExploratory studies using human fetal tissue have suggested that intrastriatal transplantation of dopaminergic neurons may become a future treatment for patients with Parkinson’s disease. However, the use of human fetal tissue is compromised by ethical, regulatory and practical concerns. Human stem cells constitute an alternative source of cells for transplantation in Parkinson’s disease, but efficient protocols for controlled dopaminergic differentiation need to be developed. Short-term, low-level carbon monoxide (CO) exposure has been shown to affect signaling in several tissues, resulting in both protection and generation of reactive oxygen species. The present study investigated the effect of CO produced by a novel CO-releasing molecule on dopaminergic differentiation of human neural stem cells. Short-term exposure to 25 ppm CO at days 0 and 4 significantly increased the relative content of β-tubulin III-immunoreactive immature neurons and tyrosine hydroxylase expressing catecholaminergic neurons, as assessed 6 days after differentiation. Also the number of microtubule associated protein 2-positive mature neurons had increased significantly. Moreover, the content of apoptotic cells (Caspase3) was reduced, whereas the expression of a cell proliferation marker (Ki67) was left unchanged. Increased expression of hypoxia inducible factor-1α and production of reactive oxygen species (ROS) in cultures exposed to CO may suggest a mechanism involving mitochondrial alterations and generation of ROS. In conclusion, the present procedure using controlled, short-term CO exposure allows efficient dopaminergic differentiation of human neural stem cells at low cost and may as such be useful for derivation of cells for experimental studies and future development of donor cells for transplantation in Parkinson’s disease.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)Instituto de Tecnologia Química e Biológica António Xavier (ITQB)RUNDreyer-Andersen, NannaAlmeida, Ana SofiaJensen, PiaKamand, MoradOkarmus, JustynaRosenberg, TineFriis, Stig DuringSerrano, Alberto MartinezBlaabjerg, MortenKristensen, Bjarne WintherSkrydstrup, TroelsGramsbergen, Jan BertVieira, Helena L. A.Meyer, Morten2018-02-16T23:17:48Z2018-01-162018-01-16T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/30670eng1932-6203PURE: 3614988https://doi.org/10.1371/journal.pone.0191207info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:16:55Zoai:run.unl.pt:10362/30670Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:29:31.109487Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Intermittent, low dose carbon monoxide exposure enhances survival and dopaminergic differentiation of human neural stem cells |
title |
Intermittent, low dose carbon monoxide exposure enhances survival and dopaminergic differentiation of human neural stem cells |
spellingShingle |
Intermittent, low dose carbon monoxide exposure enhances survival and dopaminergic differentiation of human neural stem cells Dreyer-Andersen, Nanna HEME OXYGENASE 1 FETAL NIGRAL TRANSPLANTATION HYPOXIA-INDUCIBLE FACTOR-1 ENDOTHELIAL GROWTH-FACTOR PARKINSONS-DISEASE NEURONAL DIFFERENTIATION ISCHEMIA/REPERFUSION INJURY INFLAMMATORY RESPONSE SIGNALING PATHWAYS MOLECULE-2 CORM-2 SDG 3 - Good Health and Well-being |
title_short |
Intermittent, low dose carbon monoxide exposure enhances survival and dopaminergic differentiation of human neural stem cells |
title_full |
Intermittent, low dose carbon monoxide exposure enhances survival and dopaminergic differentiation of human neural stem cells |
title_fullStr |
Intermittent, low dose carbon monoxide exposure enhances survival and dopaminergic differentiation of human neural stem cells |
title_full_unstemmed |
Intermittent, low dose carbon monoxide exposure enhances survival and dopaminergic differentiation of human neural stem cells |
title_sort |
Intermittent, low dose carbon monoxide exposure enhances survival and dopaminergic differentiation of human neural stem cells |
author |
Dreyer-Andersen, Nanna |
author_facet |
Dreyer-Andersen, Nanna Almeida, Ana Sofia Jensen, Pia Kamand, Morad Okarmus, Justyna Rosenberg, Tine Friis, Stig During Serrano, Alberto Martinez Blaabjerg, Morten Kristensen, Bjarne Winther Skrydstrup, Troels Gramsbergen, Jan Bert Vieira, Helena L. A. Meyer, Morten |
author_role |
author |
author2 |
Almeida, Ana Sofia Jensen, Pia Kamand, Morad Okarmus, Justyna Rosenberg, Tine Friis, Stig During Serrano, Alberto Martinez Blaabjerg, Morten Kristensen, Bjarne Winther Skrydstrup, Troels Gramsbergen, Jan Bert Vieira, Helena L. A. Meyer, Morten |
author2_role |
author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) Centro de Estudos de Doenças Crónicas (CEDOC) Instituto de Tecnologia Química e Biológica António Xavier (ITQB) RUN |
dc.contributor.author.fl_str_mv |
Dreyer-Andersen, Nanna Almeida, Ana Sofia Jensen, Pia Kamand, Morad Okarmus, Justyna Rosenberg, Tine Friis, Stig During Serrano, Alberto Martinez Blaabjerg, Morten Kristensen, Bjarne Winther Skrydstrup, Troels Gramsbergen, Jan Bert Vieira, Helena L. A. Meyer, Morten |
dc.subject.por.fl_str_mv |
HEME OXYGENASE 1 FETAL NIGRAL TRANSPLANTATION HYPOXIA-INDUCIBLE FACTOR-1 ENDOTHELIAL GROWTH-FACTOR PARKINSONS-DISEASE NEURONAL DIFFERENTIATION ISCHEMIA/REPERFUSION INJURY INFLAMMATORY RESPONSE SIGNALING PATHWAYS MOLECULE-2 CORM-2 SDG 3 - Good Health and Well-being |
topic |
HEME OXYGENASE 1 FETAL NIGRAL TRANSPLANTATION HYPOXIA-INDUCIBLE FACTOR-1 ENDOTHELIAL GROWTH-FACTOR PARKINSONS-DISEASE NEURONAL DIFFERENTIATION ISCHEMIA/REPERFUSION INJURY INFLAMMATORY RESPONSE SIGNALING PATHWAYS MOLECULE-2 CORM-2 SDG 3 - Good Health and Well-being |
description |
Exploratory studies using human fetal tissue have suggested that intrastriatal transplantation of dopaminergic neurons may become a future treatment for patients with Parkinson’s disease. However, the use of human fetal tissue is compromised by ethical, regulatory and practical concerns. Human stem cells constitute an alternative source of cells for transplantation in Parkinson’s disease, but efficient protocols for controlled dopaminergic differentiation need to be developed. Short-term, low-level carbon monoxide (CO) exposure has been shown to affect signaling in several tissues, resulting in both protection and generation of reactive oxygen species. The present study investigated the effect of CO produced by a novel CO-releasing molecule on dopaminergic differentiation of human neural stem cells. Short-term exposure to 25 ppm CO at days 0 and 4 significantly increased the relative content of β-tubulin III-immunoreactive immature neurons and tyrosine hydroxylase expressing catecholaminergic neurons, as assessed 6 days after differentiation. Also the number of microtubule associated protein 2-positive mature neurons had increased significantly. Moreover, the content of apoptotic cells (Caspase3) was reduced, whereas the expression of a cell proliferation marker (Ki67) was left unchanged. Increased expression of hypoxia inducible factor-1α and production of reactive oxygen species (ROS) in cultures exposed to CO may suggest a mechanism involving mitochondrial alterations and generation of ROS. In conclusion, the present procedure using controlled, short-term CO exposure allows efficient dopaminergic differentiation of human neural stem cells at low cost and may as such be useful for derivation of cells for experimental studies and future development of donor cells for transplantation in Parkinson’s disease. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-02-16T23:17:48Z 2018-01-16 2018-01-16T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/30670 |
url |
http://hdl.handle.net/10362/30670 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1932-6203 PURE: 3614988 https://doi.org/10.1371/journal.pone.0191207 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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