ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2004
The generation of dopaminergic neurons by human neural stem cells is enhanced by Bcl-XL, both in vitro and in vivo.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 93 citations in OpenAlex.
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- Survival and Neurogenesis-Promoting Effects of the Co-Overexpression ofLife (Basel, Switzerland) · 2022Article
- Neurogenesis Is Increased in Human Neural Stem Cells by Aβ40 Peptide.International journal of molecular sciences · 2022Article
- Mitochondria and Other Organelles in Neural Development and Their Potential as Therapeutic Targets in Neurodegenerative Diseases.Frontiers in neuroscience · 2022Review
- Oligomeric and Fibrillar Species of Aβ42 Diversely Affect Human Neural Stem Cells.International journal of molecular sciences · 2021Article
- Role of Liver Growth Factor (LGF) in Parkinson's Disease: Molecular Insights and Therapeutic Opportunities.Molecular neurobiology · 2021Review
- High-throughput generation of midbrain dopaminergic neuron organoids from reporter human pluripotent stem cells.STAR protocols · 2021Article
- Microglia-Secreted Factors Enhance Dopaminergic Differentiation of Tissue- and iPSC-Derived Human Neural Stem Cells.Stem cell reports · 2021Article
- Aβ42 Peptide Promotes Proliferation and Gliogenesis in Human Neural Stem Cells.Molecular neurobiology · 2019Article
- Neuronal and Glial Differentiation of Human Neural Stem Cells Is Regulated by Amyloid Precursor Protein (APP) Levels.Molecular neurobiology · 2019Article
- Nutritional Regulators of Bcl-xL in the Brain.Molecules (Basel, Switzerland) · 2018Review
- Roles of neural stem cells in the repair of peripheral nerve injury.Neural regeneration research · 2017Review
- Directed Differentiation of Dopamine-Secreting Cells from Nurr1/GPX1 Expressing Murine Embryonic Stem Cells Cultured on Matrigel-Coated PCL Scaffolds.Molecular neurobiology · 2017Article
- A Compendium of Preparation and Application of Stem Cells in Parkinson's Disease: Current Status and Future Prospects.Frontiers in aging neuroscience · 2016Review
- Survival, differentiation, and neuroprotective mechanisms of human stem cells complexed with neurotrophin-3-releasing pharmacologically active microcarriers in an ex vivo model of Parkinson's disease.Stem cells translational medicine · 2015Article
- Proceedings: cell therapies for Parkinson's disease from discovery to clinic.Stem cells translational medicine · 2014Article
- Influence of oxygen tension on dopaminergic differentiation of human fetal stem cells of midbrain and forebrain origin.PloS one · 2014Article
- Neuroprotective activity of peripherally administered liver growth factor in a rat model of Parkinson's disease.PloS one · 2013Article
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3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Progress in stem cell biology research is enhancing our ability to generate specific neuron types for basic and applied studies and to design new treatments for neurodegenerative diseases. In the case of Parkinson's disease (PD), alternative human dopaminergic (DAergic) neurons other than primary fetal tissue do not yet exist. One possible source could be human neural stem cells (hNSCs), although the yield in DAergic neurons and their survival are very limited. [see figure]. In this study, we found that Bcl-X(L) enhances (one-to-two orders of magnitude) the capacity for spontaneous dopaminergic differentiation of hNSCs, which then exceeds that of cultured human ventral mesencephalic tissue. Bcl-X(L) also enhanced total neuron generation by hNSCs, but to a lower extent. Neuronal phenotypes other than DA were not affected by Bcl-X(L), indicating an exquisitely specific effect on DAergic neurons. In vivo, grafts of Bcl-X(L)-overexpressing hNSCs do generate surviving human TH+ neurons in the adult rat 6-OH-dopamine lesioned striatum, something never seen when naive hNSCs were transplanted. Most of the data obtained here in terms of the effects of Bcl-X(L) are consistent with an enhanced survival type of mechanism and not supportive of induction, specification, or proliferation of DAergic precursors. From this in vitro and in vivo evidence, we conclude that enhancing Bcl-X(L) expression is important to obtain human DAergic neurons from hNSCs. These findings may facilitate the development of drug-screening and cell-replacement activities to discover new therapeutic strategies for PD.
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