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

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 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Translational Psychiatry Springer Journals

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

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Publisher
Nature Publishing Group UK
Copyright
Copyright © 2018 by The Author(s)
Subject
Medicine & Public Health; Medicine/Public Health, general; Psychiatry; Neurosciences; Behavioral Sciences; Pharmacotherapy; Biological Psychology
eISSN
2158-3188
D.O.I.
10.1038/s41398-018-0095-9
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

Translational PsychiatrySpringer Journals

Published: Feb 22, 2018

References

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