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Pharmacological Transdifferentiation of Human Nasal Olfactory Stem Cells into Dopaminergic Neurons
- Source :
- Stem Cells International, Stem Cells International, 2019, 2019, pp.eCollection 2019. ⟨10.1155/2019/2945435⟩, Stem Cells International, Hindawi Publishing Corporation, 2019, 2019, pp.eCollection 2019. ⟨10.1155/2019/2945435⟩, Stem Cells International, Vol 2019 (2019)
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Abstract
- The discovery of novel drugs for neurodegenerative diseases has been a real challenge over the last decades. The development of patient- and/or disease-specificin vitromodels represents a powerful strategy for the development and validation of lead candidates in preclinical settings. The implementation of a reliable platform modeling dopaminergic neurons will be an asset in the study of dopamine-associated pathologies such as Parkinson’s disease. Disease models based on cell reprogramming strategies, using either human-induced pluripotent stem cells or transcription factor-mediated transdifferentiation, are among the most investigated strategies. However, multipotent adult stem cells remain of high interest to devise direct conversion protocols and establishin vitromodels that could bypass certain limitations associated with reprogramming strategies. Here, we report the development of a six-step chemically defined protocol that drives the transdifferentiation of human nasal olfactory stem cells into dopaminergic neurons. Morphological changes were progressively accompanied by modifications matching transcript and protein dopaminergic signatures such as LIM homeobox transcription factor 1 alpha (LMX1A), LMX1B, and tyrosine hydroxylase (TH) expression, within 42 days of differentiation. Phenotypic changes were confirmed by the production of dopamine from differentiated neurons. This new strategy paves the way to develop more disease-relevant models by establishing reprogramming-free patient-specific dopaminergic cell models for drug screening and/or target validation for neurodegenerative diseases.
- Subjects :
- 0301 basic medicine
lcsh:Internal medicine
Article Subject
[SDV]Life Sciences [q-bio]
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Biology
03 medical and health sciences
0302 clinical medicine
Dopaminergic Cell
[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
lcsh:RC31-1245
Induced pluripotent stem cell
[SDV.BC] Life Sciences [q-bio]/Cellular Biology
Molecular Biology
ComputingMilieux_MISCELLANEOUS
Tyrosine hydroxylase
Dopaminergic
Transdifferentiation
[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Cell Biology
[SDV] Life Sciences [q-bio]
030104 developmental biology
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Stem cell
Neuroscience
Reprogramming
030217 neurology & neurosurgery
Research Article
Adult stem cell
Subjects
Details
- Language :
- English
- ISSN :
- 16879678 and 1687966X
- Volume :
- 2019
- Database :
- OpenAIRE
- Journal :
- Stem Cells International
- Accession number :
- edsair.doi.dedup.....9c9f84bd723dfc451a150640099319f3
- Full Text :
- https://doi.org/10.1155/2019/2945435