hiPSC-derived neural stem cells from patients with schizophrenia induce an impaired angiogenesis

Schizophrenia is a neurodevelopmental disease characterized by cerebral connectivity impairment and loss of gray matter. It was described in adult schizophrenia patients (SZP) that concentration of VEGFA, a master angiogenic factor, is decreased. Recent evidence suggests cerebral hypoperfusion relat...

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Bibliographic Details
Published in:Translational psychiatry 2018-02, Vol.8 (1), p.48-15, Article 48
Main Authors: Casas, Bárbara S., Vitória, Gabriela, do Costa, Marcelo N., Madeiro da Costa, Rodrigo, Trindade, Pablo, Maciel, Renata, Navarrete, Nelson, Rehen, Stevens K., Palma, Verónica
Format: Article
Language:English
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Angiogenesis
Angiogenesis Inducing Agents - metabolism
Behavioral Sciences
Biological Psychology
Female
Humans
Induced Pluripotent Stem Cells - metabolism
Induced Pluripotent Stem Cells - physiology
Male
Medicine
Medicine & Public Health
Neovascularization, Pathologic - metabolism
Neovascularization, Pathologic - physiopathology
Neural Stem Cells - metabolism
Neural Stem Cells - physiology
Neurogenesis - physiology
Neurosciences
Pharmacotherapy
Psychiatry
Schizophrenia
Schizophrenia - metabolism
Schizophrenia - physiopathology
Stem cells
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Summary:Schizophrenia is a neurodevelopmental disease characterized by cerebral connectivity impairment and loss of gray matter. It was described in adult schizophrenia patients (SZP) that concentration of VEGFA, a master angiogenic factor, is decreased. Recent evidence suggests cerebral hypoperfusion related to a dysfunctional Blood Brain Barrier (BBB) in SZP. Since neurogenesis and blood-vessel formation occur in a coincident and coordinated fashion, a defect in neurovascular development could result in increased vascular permeability and, therefore, in poor functionality of the SZP’s neurons. Here, we characterized the conditioned media (CM) of human induced Pluripotent Stem Cells (hiPSC)-derived Neural Stem Cells of SZP (SZP NSC) versus healthy subjects (Ctrl NSC), and its impact on angiogenesis. Our results reveal that SZP NSC have an imbalance in the secretion and expression of several angiogenic factors, among them non-canonical neuro-angiogenic guidance factors. SZP NSC migrated less and their CM was less effective in inducing migration and angiogenesis both in vitro and in vivo . Since SZP originates during embryonic brain development, our findings suggest a defective crosstalk between NSC and endothelial cells (EC) during the formation of the neuro-angiogenic niche.
ISSN:2158-3188
2158-3188
DOI:10.1038/s41398-018-0095-9