Intermittent, low dose carbon monoxide exposure enhances survival and dopaminergic differentiation of human neural stem cells.
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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5770048?pdf=render |
| _version_ | 1818268651184193536 |
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| author | Nanna Dreyer-Andersen Ana Sofia Almeida Pia Jensen Morad Kamand Justyna Okarmus Tine Rosenberg Stig Düring Friis Alberto Martínez Serrano Morten Blaabjerg Bjarne Winther Kristensen Troels Skrydstrup Jan Bert Gramsbergen Helena L A Vieira Morten Meyer |
| author_facet | Nanna Dreyer-Andersen Ana Sofia Almeida Pia Jensen Morad Kamand Justyna Okarmus Tine Rosenberg Stig Düring Friis Alberto Martínez Serrano Morten Blaabjerg Bjarne Winther Kristensen Troels Skrydstrup Jan Bert Gramsbergen Helena L A Vieira Morten Meyer |
| author_sort | Nanna Dreyer-Andersen |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-12T20:41:52Z |
| format | Article |
| id | doaj.art-f954a8cfff114e9b8cbb04544d320bc9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T20:41:52Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f954a8cfff114e9b8cbb04544d320bc92022-12-22T00:12:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01131e019120710.1371/journal.pone.0191207Intermittent, low dose carbon monoxide exposure enhances survival and dopaminergic differentiation of human neural stem cells.Nanna Dreyer-AndersenAna Sofia AlmeidaPia JensenMorad KamandJustyna OkarmusTine RosenbergStig Düring FriisAlberto Martínez SerranoMorten BlaabjergBjarne Winther KristensenTroels SkrydstrupJan Bert GramsbergenHelena L A VieiraMorten MeyerExploratory 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.http://europepmc.org/articles/PMC5770048?pdf=render |
| spellingShingle | Nanna Dreyer-Andersen Ana Sofia Almeida Pia Jensen Morad Kamand Justyna Okarmus Tine Rosenberg Stig Düring Friis Alberto Martínez Serrano Morten Blaabjerg Bjarne Winther Kristensen Troels Skrydstrup Jan Bert Gramsbergen Helena L A Vieira Morten Meyer Intermittent, low dose carbon monoxide exposure enhances survival and dopaminergic differentiation of human neural stem cells. PLoS ONE |
| title | 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_short | 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 |
| url | http://europepmc.org/articles/PMC5770048?pdf=render |
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